Progress 10/01/12 to 03/31/16
Outputs
Target Audience:Results from this project were disseminated through abstracts, papers (previously cited), and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: UC ANR Workgroup on Livestock Production Systems. TARGET AUDIENCES: American Physiological Society, Comparative Physiology Section. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?Scientific results and data from this project were published and made available (through abstracts, full papers, and seminars) to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
1. Elucidation of the pulmonary mechanisms involved in microcirculatory/interstitial/lymphatic control of lung fluid balance in the domestic chicken (Gallus domesticus). 2. Validation of an isolated avian lung model for the study of pulmonary vascular regulation of lung fluid balance in birds. 3. Elucidation of data allowed the comparison of avian physiological and anatomical safety factors against pulmonary edema with similar mammalian mechanisms. OUTPUTS: 1. Studies conducted in the PIs laboratory were relevant to the goals and objectives of this project with respect to the description of physiological and pathophysiological processes associated with avian respiratory and pulmonary vascular diseases such as broiler disease, bacteremia, and acute pulmonary hemorrhage caused by toxic molds. Studies in the domestic chicken (gallus domesticus) relevant to the elucidation of mechanisms producing the pathophysiology of avian broiler disease and bacteremia associated with colibacillosis were completed. Results from these studies are consistent with previously reported data on the control of lung fluid balance in the pulmonary microcirculation in poultry. Theses studies utilized a model established in the PI's laboratory which mimicked the edemogenic respiratory distress observed in broiler disease. These results were disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine.
Publications
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Progress 10/01/13 to 09/30/14
Outputs
Target Audience: American Physiological Society (Comparative Physiology Section) Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest? Results of studies were disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Studies in the domestic chicken (gallus domesticus) relevant to the elucidation of mechanisms producing the pathophysiology of avian broiler disease and bacteremia associated with colibacillosis were completed. Results from these studies are consistent with previously reported data on the control of lung fluid balance in the pulmonary microcirculation in poultry. Theses studies utilized a model established in the PI's laboratory which mimics the edemogenic respiratory distress observed in broiler disease. These preliminary results from this model were disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: UC ANR Workgroup on Livestock Production Systems. TARGET AUDIENCES: American Physiological Society, Comparative Physiology Section PROJECT MODIFICATIONS: Not relevant to this project.
Publications
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Progress 01/01/13 to 09/30/13
Outputs
Target Audience: American Physiological Society, Comparative Physiology Section Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest? These preliminary results have been disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: UC ANR Workgroup on Livestock Production Systems. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
The results of this research suggest 1) that in poultry lung microvascular permeability is increased by substances which mimic the effects of avian broiler disease; 2) that the expression of lung endothelial adhesion proteins is altered during the pathophysiological eitiology of broiler disease, that 3) birds are protected against pulmonary edema by microcirculatory mechanisms, which while uniquely avian, are similar to those found in mammals, and 4) based on my most recent studies, that differential regional distribution of pulmonary blood flow in the avian lung may contribute to this safety factor. Support from this Hatch project has been essential to the acquisition of advanced software used in experimental data collection and real-time analysis. This information suggests that therapies and clinical interventions used in mammals against pulmonary edema resulting from increased lung microvascular permeability associated with altered endothelial adhesion protein function may also be efficacious in birds. These results are relevant to poultry husbandry, comparative and microvascular physiology, and avian and exotic veterinary medicine.
Publications
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Progress 01/01/12 to 12/31/12
Outputs
OUTPUTS: Studies continue in the domestic chicken (gallus domesticus) relevant to the elucidation of mechanisms producing the pathophysiology of avian broiler disease and bacteremia associated with colibacillosis. Results from these studies are consistent with previously reported data on the control of lung fluid balance in the pulmonary microcirculation in poultry. To date theses studies have utilized a procedure established in the PI's laboratory which mimics the edemogenic respiratory distress observed in broiler disease. These preliminary results have been disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: UC ANR Workgroup on Livestock Production Systems. TARGET AUDIENCES: American Physiological Society, Comparative Physiology Section PROJECT MODIFICATIONS: Not relevant to this project. PARTICIPANTS: Partner Organization: UC ANR Workgroup on Livestock Production Systems Training opportunities: Three pre-veterinary medicine students received research training on this project. TARGET AUDIENCES: TARGET AUDIENCES: American Physiological Society, Comparative Physiology Section PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The results of this research suggest 1) that in poultry lung microvascular permeability is increased by substances which mimic the effects of avian broiler disease; 2) that the expression of lung endothelial adhesion proteins is altered during the pathophysiological eitiology of broiler disease, that 3) birds are protected against pulmonary edema by microcirculatory mechanisms, which while uniquely avian, are similar to those found in mammals, and 4) based on my most recent studies, that differential regional distribution of pulmonary blood flow in the avian lung may contribute to this safety factor. Support from this Hatch project has been essential to the acquisition of advanced software used in experimental data collection and real-time analysis. This information suggests that therapies and clinical interventions used in mammals against pulmonary edema resulting from increased lung microvascular permeability associated with altered endothelial adhesion protein function may also be efficacious in birds. These results are relevant to poultry husbandry, comparative and microvascular physiology, and avian and exotic veterinary medicine.
Publications
- Weidner WJ, Bradbury CA, Le SP, and Wallace SR (2012) Regional Pulmonary Blood Flow in the lung of the Chicken. Poultry Science 6: 1441-3.
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Progress 01/01/11 to 12/31/11
Outputs
OUTPUTS: Studies continue in the domestic chicken (gallus domesticus) relevant to the elucidation of mechanisms producing the pathophysiology of avian broiler disease and bacteremia associated with colibacillosis. Results from these studies are consistent with previously reported data on the control of lung fluid balance in the pulmonary microcirculation in poultry. To date theses studies have utilized a procedure established in the PI's laboratory which mimics the edemogenic respiratory distress observed in broiler disease. These preliminary results have been disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: American Physiological Society, Comparative Physiology Section PROJECT MODIFICATIONS: Not relevant to this project. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: American Physiological Society, Comparative Physiology Section PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The results of this research suggest 1) that in poultry lung microvascular permeability is increased by substances which mimic the effects of avian broiler disease; 2) that the expression of lung endothelial adhesion proteins is altered during the pathophysiological eitiology of broiler disease, that 3) birds are protected against pulmonary edema by microcirculatory mechanisms, which while uniquely avian, are similar to those found in mammals, and 4) based on my most recent studies, that differential regional distribution of pulmonary blood flow in the avian lung may contribute to this safety factor. Support from this Hatch project has been essential to the acquisition of advanced software used in experimental data collection and real-time analysis. This information suggests that therapies and clinical interventions used in mammals against pulmonary edema resulting from increased lung microvascular permeability associated with altered endothelial adhesion protein function may also be efficacious in birds. These results are relevant to poultry husbandry, comparative and microvascular physiology, and avian and exotic veterinary medicine.
Publications
- W. Jeffrey Weidner. Effects of hypoxia and hypercapnia on neopulmonic and paleopulmonic pulmonary blood flow in Gallus domesticus. Trends in Comp. Biochem. and Physiol. www.researchtrends/RT/CBP/192 2011.
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Progress 01/01/10 to 12/31/10
Outputs
OUTPUTS: Studies continue in the domestic chicken (gallus domesticus) relevant to the elucidation of mechanisms producing the pathophysiology of avian broiler disease and bacteremia associated with colibacillosis. Results from these studies are consistent with previously reported data on the control of lung fluid balance in the pulmonary microcirculation in poultry. To date theses studies have utilized a procedure established in the PI's laboratory which mimics the edemogenic respiratory distress observed in broiler disease. These preliminary results have been disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Experimental Biology 2010, American Physiological Society, Comparative Physiology Section seminar: New Insights into the Pulmonary circulation, Invited Seminar: Avian Lung Fluid Balance: Studies in the Chicken, April 29, 2010. PROJECT MODIFICATIONS: Not relevant to this project. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Experimental Biology 2010, American Physiological Society, Comparative Physiology Section seminar: New Insights into the Pulmonary circulation, Invited Seminar: Avian Lung Fluid Balance: Studies in the Chicken, April 29, 2010 PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The results of this research suggest 1) that in poultry lung microvascular permeability is increased by substances which mimic the effects of avian broiler disease; 2) that the expression of lung endothelial adhesion proteins is altered during the pathophysiological eitiology of broiler disease and that 3) birds are protected against pulmonary edema by microcirculatory mechanisms, which while uniquely avian, are similar to those found in mammals. Support for this Hatch project was essential to the aquissition of advanced software used in experimental data collection and real-time analysis. This information suggests that therapies and clinical interventions used in mammals against pulmonary edema resulting from increased lung microvascular permeability associated with altered endothelial adhesion protein function may also be efficacious in birds. These results are relevant to poultry husbandry, comparative and microvascular physiology, and avian and exotic veterinary medicine.
Publications
- No publications reported this period
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: Studies on the mechanisms contributing to the control of avian lung fluid balance relevant to the pathophysiology of avian broiler disease and bacteremia continue using the chicken (Gallus domesticus) as a model. Results of recent experiments are consistent with previously reported data from this Hatch Project on the control of transvascular fluid movement in the pulmonary microcirculation in a model developed in the PI's laboratory which mimics the edemogenic respiratory distress and ascites seen in avian broiler disease and bacteremia associated with colibasillosis. Results suggest that increases in the pulmonary microcirculatory capillary filtration coefficient and osmotic reflection coefficient for protein are correlated with changes in the expression of pulmonary endothelial cadherin adhesion proteins at adherens junctions. Results of these studies have been disseminated through publications, seminars, research presentations, and colloquia to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine in this country and abroad. PARTICPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The results of this research suggest that in poultry 1) lung microvascular permeability is increased by substances which mimic the effects of avian boiler disease and bacteremia; 2) that the expression of endothelial adhesion proteins is altered by substances which mimic the effect of avian broiler disease and bacteremia; and, that 3) lung safety factors similar to those found in mammals, yet uniquely avian, protect birds against the development of pulmonary edema. Support for this Hatch Project was essential in the acquisition of an advanced computer system in the PI's laboratory used in data collection and real time analysis. Work conducted in this project suggests that therapeutic and clinical interventions used to prevent and/or treat lung edema resulting from increased pulmonary microvascular permeability to fluid and protein in mammals may also be efficacious in birds. The results of these studies are relevant to the fields of poultry husbandry, comparative and cardiovascular physiology, and avian and exotic veterinary medicine.
Publications
- No publications reported this period
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: Studies continue in the domestic chicken (gallus domesticus) relevant to the elucidation of mechanisms producing the pathophysiology of avian broiler disease. Preliminary results from these studies are consistent with previously reported data from this Hatch Project on the control of lung fluid balance in the pulmonary microcirculation in poultry. Pulmonary capillary permeability was increased in anesthetized chickens utilizing a procedure established in the PI's laboratory which mimics the edemogenic respiratory distress observed in broiler disease. Administration of oleic acid (OA) or dimethyl amiloride (DMA), substances which alter lung fluid balance by different and distinct cellular mechanisms, increased the pulmonary capillary filtration coefficient. DMA but not OA administration resulted in increased expression of lung vascular endothelial cadherin (CAD 5 or VE cadherin) an adhesion molecule involved in the regulation of microcirculatory porosity in the vertebrate lung. These preliminary results have been disseminated through abstracts and seminars to researchers and clinicians in associated fields of study and interest, such as cardiopulmonary and comparative physiology and avian and exotic veterinary medicine. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The results of this research suggest 1) that in poultry lung microvascular permeability is increased by substances which mimic the effects of avian broiler disease; 2) that the expression of lung endothelial adhesion proteins is altered during the pathophysiological eitiology of broiler disease and that 3) birds are protected against pulmonary edema by microcirculatory mechanisms, which while uniquely avian, are similar to those found in mammals. Support for this Hatch project was essential to the development of an advanced computer program in the PI's laboratory used in experimental data collection and real-time analysis. This information suggests that therapies and clinical interventions used in mammals against pulmonary edema resulting from increased lung microvascular permeability associated with altered endothelial adhesion protein function may also be efficacious in birds. These results are relevant to poultry husbandry, comparative and microvascular physiology, and avian and exotic veterinary medicine.
Publications
- WJ Weidner (2008) Field of Physiology: Themes in research and innovation. Program of the Gaspar de Portola Institute. California/Catalonia, Scientific and Academic Relationships. Director General of Research. Generalitat of Catalonia. www.gencat.net/recerca/temesri/
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Progress 01/01/07 to 12/31/07
Outputs
Studies have been completed in the chicken (Gallus domesticus) relevant to the pathophysiology of broiler disease which are consistent with previously reported data from this Hatch Project on the control of lung fluid balance at the level of the pulmonary microcirculation in poultry. Pulmonary capillary permeability was increased in chickens to mimic edemogenic respiratory distress seen in broiler disease by administration of dimethyl amiloride (DMA), a substance which induces pulmonary edema by altering lung epithelial Na plus transport. In these chickens the pulmonary capillary filtration coefficient (Kf), which was directly measured by a new and unique method developed in my laboratory, increased to 0.74 plus minus 0.14 ml/min/cmH2O/100g and was significantly higher than the Kf of 0.38 plus minus .09 ml/min/cmH2O/100g seen in normal control chickens. Additional data from Western and Northern immunoblot studies confirm that endothelial cadherins play an important role
in the short term regulation of pulmonary capillary permeability under both normal and pathophysiological conditions.
Impacts
The results of this research suggest 1) that in chickens lung microvascular permeability is increased by substances which mimic the pulmonary effects of broiler disease; 2) that the expression of endothelial adhesion molecules is altered in chickens during increased lung microvascular permeability mimicking the effects of broiler disease; and 3) that birds are protected against pulmonary edema by microcirculatory mechanisms which are similar to those in mammals. This information suggests that therapies used in mammals against pulmonary edema may also be efficacious in birds. These results are relevant to poultry husbandry, comparative physiology, and in particular avian veterinary medicine.
Publications
- WJ Weidner (2007) Ambit de Fisiologia: Temes de Recerca i Innovacio. Generalitat de Catalunya. Direccio General de Recerca. Num. 2: 36-38.
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Progress 01/01/06 to 12/31/06
Outputs
Studies have been completed in the chicken (Gallus domesticus) which are consistent with previously reported data from this Hatch Project and are relevant to the control of lung fluid balance at the level of the pulmonary microcirculation. In these studies the pulmonary capillary filtration coefficient (Kf) was directly measured by a new and unique method developed in my laboratory. The value of Kf found in these studies for the normal anesthetized chicken is 0.38 plus or minus .09 ml/min/cmH2O/100g. In other chickens increased pulmonary capillary permeability was induced to mimic edemogenic respiratory distress such as caused by collibacillosis by administration of oleic acid. In these chickens Kf increased to 1.14 plus or minus 0.14 ml/min/cmH2O/100g. Western and Northern immunoblot data from this study confirm that endothelial cadherins play an important role in the short term regulation of pulmonary capillary permeability under both normal and pathophysiological
conditions.
Impacts
The results of this research suggest 1) that birds are protected against pulmonary edema by microcirculatory mechanisms which are similar to those in mammals; 2) that endothelial adhesion molecules are important in the regulation of avian pulmonary microvascular permeability; and 3) that the filtration characteristics of the avian lung are more mammalian than reptilian. This information suggests that therapies used in mammals against pulmonary edema may also be efficacious in birds. These results are relevant to poultry husbandry, comparative physiology, and in particular avian veterinary medicine.
Publications
- WJ Weidner, DS Waddell, JD Furlow (2006) Measurement of the filtration coefficient (Kfc) in the lung of Gallus domesticus and the effects of increased microvascualr permeability. J. Comp. Physiol. B 176: 567-574.
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Progress 01/01/05 to 12/31/05
Outputs
Studies have been completed in Gallus domesticus in which suggest the pulmonary capillary filtration coefficient (Kf) of the avian lung was directly measured. The value of Kf found in these studies for the normal anesthetized chicken (0.38 + or - .09 ml/min/cmH2O/100g) is consistent with values reported in several mammalian species and is well below values reported for the amphibian and reptile lung. Experimentally induced damage to the pulmonary endothelium increased Kf to 1.14 + or - 0.14 ml/min/cmH2O/100g. This is consistent with studies in similarly prepared mammalian lungs. Western and Northern Immunoblot data from this study confirms that, as has been reported for mammals, endothelial cadherins play an important role in determining the permeability characteristics of the avian pulmonary microcirculation.
Impacts
The results of this study are consistent with earlier work from my laboratory which suggests that birds are protected against pulmonary edema by microcirculatory mechanisms which are similar to those in mammals. These results are relevant to poultry husbandry, veterinary medicine, and comparative physiology in general.
Publications
- No publications reported this period
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Progress 01/01/04 to 12/31/04
Outputs
Studies have been completed in Gallus domesticus in which suggest the pulmonary capillary filtration coefficient (Kf) of the avian lung was directly measured. The value of Kf found in these studies for the normal anesthetized chicken (0.38 + or - .09 ml/min/cmH2O/100g) is consistent with values reported in several mammalian species and is well below values reported for the amphibian and reptile lung. Immunoblot data from this study suggests that, as has been reported for mammals, endothelial cadherins play an important role in determining the permeability characteristics of the avian pulmonary microcirculation.
Impacts
The results of this study are consistent with earlier work from my laboratory which suggests that birds are protected against pulmonary edema by microcirculatory mechanisms which are similar to those in mammals. These results are relevant to poultry husbandry, veterinary medicine, and comparative physiology in general.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
Studies have been completed which utilized scanning electron microscopy (SEM) to examine the interparabronchial septum as a potential site of lymphatic drainage in the lungs of anesthetized chickens (Gallus domesticus) subjected to moderate and extreme volume loading in order to produce pulmonary edema. In both conditions adjacent parabronchi of normal control lungs were closely opposed by a minimal septal space while those of volume loaded birds were measurably thickened and engorged. The results of this study are consistent with data from mammals and suggest that the interparabronchial septum may be a potential route of lymphatic drainage in the avian lung.
Impacts
The results of this research suggest that birds may be protected against pulmonary edema by mechanisms which are similar to those in mammals. Particularly with respect to the role of loose interstitial spaces serving as routes of lymphatic drainage or as potential spaces for fluid accumulation outside of the gas-exchanging region of the lung. The studies are relevant to poultry husbandry, avian veterinary medicine, and comparative pulmonary physiology in general.
Publications
- Weidner, WJ, SR Lau, and S Wallace (2003) Measurement of the capillary filtration coefficient in the isolated perfused avian lung. FASEB J. 17: A935.
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Progress 01/01/02 to 12/31/02
Outputs
Studies have been completed which utilized scanning electron microscopy (SEM) to examine the interparabronchial septum as a potential site of lymphatic drainage in the lungs of anesthetized chickens (Gallus domesticus) subjected to moderate and extreme volume loading in order to produce pulmonary edema. In both conditions adjacent parabronchi of normal control lungs were closely opposed by a minimal septal space while those of volume loaded birds were measurably thickened and engorged. The results of this study are consistent with data from mammals and suggest that the interparabronchial septum may be a potential route of lymphatic drainage in the avian lung. Two papers have been published. Two additional papers are in prepartion . An abstract has been submitted for presenation at the Experimantal Biology 2003 meeting in April.
Impacts
The results of this research suggest that birds may be protected against pulmonary edema by mechanisms which are similar to those in mammals. Particularly with respect to the role of loose interstitial spaces serving as routes of lymphatic drainage or as potential spaces for fluid accumulation outside of the gas-exchanging region of the lung. The studies are relevant to poultry husbandry, avian veterinary medicine, and comparative pulmonary physiology in general.
Publications
- Weidner, W.J. and J.R. Kinnison. Effect of hydrostatic pulmonary edema on the intraparabronchial septum of the chicken lung. Poultry Science 81: 1563-1566, 2002.
- Weidner, W.J. and J.R. Kinnison. Effect of extracellular fluid volume expansion on the intraparabronchial septum of the avian lung. J. Comp. Path. 127: 219-222, 2002.
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Progress 01/01/01 to 12/31/01
Outputs
Studies have been completed which utilized scanning electron microscopy (SEM) to examine the interparabronchial septum as a potential site of lymphatic drainage in the lungs of anesthetized chickens (Gallus domesticus) subjected to moderate and extreme volume loading in order to produce pulmonary edema. In both conditions adjacent parabronchi of normal control lungs were closely opposed by a minimal septal space while those of volume loaded birds were measurably thickened and engorged. The results of this study are consistent with data from mammals and suggest that the interparabronchial septum may be a potential route of lymphatic drainage in the avian lung. An additional study reports that the visceral air sac mesothelium of volume loaded chickens presents an increased density of bulbous or swollen microvilli as compared to controls. This is also similar to changes observed in the visceral pleura of mammals subjected to hydrothorax. Two manuscripts have been
submitted for publication.
Impacts
The results of this research suggest that birds may be protected against pulmonary edema by mechanisms which are similar to those in mammals. Particularly with respect to the role of loose interstitial spaces serving as routes of lymphatic drainage or as potential spaces for fluid accumulation outside of the gas-exchanging region of the lung. The studies are relevant to poultry husbandry, avian veterinary medicine, and comparative pulmonary physiology in general.
Publications
- Weidner, WJ (2000) Response of air sac mesothelium to expansion of extracellular fluid volume in Gallus domesticus. J. Comp. Path. 123: 182-185
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Progress 01/01/00 to 12/31/00
Outputs
Studies have been completed which show that the edemogenic effects of a number of agents in the lung of Gallus domesticus are related to the disruption of cadherin adhesion molecule activity at cites of cell-to-cell contact (adherens junctions) in the pulmonary endothelium. I intend to utilize similar techniques to examine the expression of cadherin - complex adhesion molecules in the lungs of immature and mature Broiler chickens and to compare these data to those obtained from normal White leghorn chicks and adults. Ongoing studies in my laboratory in the area of avian lung fluid balance include experiments designed 1) to measure the pulmonary capillary filtration coefficient (Kf), an important component of lung fluid balance, and 2) to examine the mechanism of lung lymphatic drainage in the lung of Gallus, an important safety factor against edema. Preliminary results suggest that Kf in the lung of Gallus is similar to that reported for mammals (in the range 0.3 -
0.8 ml/min/CmH2O/100g tissue weight), but that the mechanism of lymphatic drainage may be anatomically much different than found in mammals in that the interparabronchial septal space as well as air sac mesothelium may partcipate in lymphatic removal from the lung. These structures are not found in mammals.
Impacts
The basic physiology and pathophysiology of lung fluid balance in Gallus is relevant to the poultry breeding industry in that respiratory diseases are a leading cause of flock mortality. This is particularly true of Broiler husbandry. The underlying mechanisms of many avian respiratory diseases, and hence their prevention, may involve pathophysiological mechanisms which alter normal lung fluid balance.
Publications
- WEIDNER, W.J. and LANCASTER, C.T. 1999. Effects of monastral blue on pulmonary arterial blood pressure and lung and liver particle retention in chickens. Poultry Science 78:878-882.
- WEIDNER, W.J. 2000. Response of air sac mesothelium to expansion of extracellular fluid volume in gallus domesticus. J. Comparative Pathology. 123: in press.
- WEIDNER, W.J. and SILLMAN, A.J. 2000. Low levels of cadmium chloride alter the immunoprecipitation of corneal cadherin-complex proteins. Arch. Toxicol. in press.
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Progress 01/01/99 to 12/31/99
Outputs
Studies have been completed which utilized scanning electron microscopy (SEM) to examine the interparabronchial septum as a potential site of lymphatic drainage in the lungs of anesthetized chickens (Gallus domesticus) subjected to volume loading in order to produce pulmonary edema. The adjacent parabronchi of normal control were closely opposed by a minimal septal space while those of volume loaded birds were measurably thickened and engorged. The results of this study are consistent with data from mammals and suggest that the interparabronchial septum may be a potential route of lymphatic drainage in the avian lung. Related SEM studies show that the visceral air sac mesothelium of volume loaded chickens presents an increased density of bulbous or swollen microvilli as compared to controls. This is also similar changes observed in the visceral pleura of mammals subjected to hydrothorax. An additional study that assessed the response of anesthetized chickens to
intravenous administration of Monastral blue suggests that chickens do not possess reactive pulmonary intravascular macrophages (PIMS) as do certain mammals.
Impacts
The results of this research suggest that 1) birds may be protected against pulmonary edema by mechanisms which are similar to those in mammals, and 2) the lack of PIMS in galliform birds may in part explain the virulence of respiratory diseases such as colibacilosis in poultry. The studies are relevant to poultry husbandry, avian veterinary medicine, and comparative pulmonary physiology in general.
Publications
- Weidner, W.J. and Lancaster, C.T. 1999. Effects of monastral blue on pulmonary arterial blood pressure and lung and liver particle retention in chickens. Poultry Science 78:878-882.
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Progress 01/01/98 to 12/01/98
Outputs
Studies have been completed which utilized Western blot analysis and enhanced chemoluminescence to examine the effects of thrombin (T), phorbol myristate acetate (PMA), dimethyl amiloride (DMA), and the heavy metal cadmium (Cd) on vascular and corneal endothelial cadherin activity. Cadherins are calcium dependent adhesion proteins which play an important role in the regulation of intercellular permeability. Chicken lung, heart, and pulmonary artery showed increased cadherin immunoprecipitation in response to T and PMA, while in animals treated with DMA, a potent inhibitor of the cellular sodium/proton antiport system, cadherin immunoprecipitation was diminished or absent. We are currently using immuno-electron microscopy to localize the effect to the VE (vascular endothelial)-cadherin at the tight junctions of the microvascular endothium in the above tissues. In the corneal endothelium Cd appears to decrease the immunoprecipitation of cadherins and the associated
regulatory proteins, alpha and beta catenin, and recent evidence suggests that this effect may be associated with altered protein phosphorylation. We believe that the altered cadherin complex activity may in part underlie the effects of these agents on endothelial permeability in the above tissues.
Impacts
(N/A)
Publications
- WEIDNER, W.J. and WADDELL, D.S. Decreased cadherin immunoprecipitation induced by dimethyl amiloride (DMA) in avian
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Progress 01/01/97 to 12/01/97
Outputs
The most important results of this project for the reporting period were the observations that thrombin (T), phorbol myristate acetate (PMA), and the heavy metals cadmium (Cd) and mercury (Hg) appear to alter the immunoprecipitation of cadherins, alpha and beta catenins, and phosphotyrosine in the adhesion molecule complex. Chicken lung, heart, and pulmonary artery were examined by Western Blot analysis. Each tissue showed increased cadherin complex activity associated with increased phosphorylation following T or PMA. Cd and Hg appear to decrease cadherin complex immunoprecipitation in the corneal endothelium and this may be associated with altered protein phosphorylation when exposure to the heavy metals is at low doses (- 1.0 micromolar). Since cadherins as adhesion molecules are thought to play an important role in the formation of endothelial intercellular adherens junctions, we believe that altered cadherin complex activity may underlie the effects of these
agents on endothelial permeability. We have recently begun to use enhanced chemoluminescence (ECL) to further examine the effects of T, PMA, Cd and Hg on endothelial permeability in the above tissues.
Impacts
(N/A)
Publications
- WEIDNER, W.J., WADDELL, D.S., MILES, M.S. and HAGGERTY, K. 1997. Increased cadherin immunoprecipitation induced by phorbol myristate acetate (PMA) and thrombin (T) in avian lung and heart. FASEB J. 11:
- WEIDNER, W.J. and SILLMAN, A.J. 1997. Low levels of cadmium chloride damage the corneal endothelium. Arch. Toxicol. 71: 455-460.
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Progress 01/01/96 to 12/30/96
Outputs
The most important results of this project for the reporting period were the observation that thrombin (T) and phorbol myristate acetate (PMA) appear to increase the expression of a vascular endothelial cadherin in both lung and heart. Cadherins are adhesion molecules and play an important role in intercellular permeability. T and PMA increase endothelial permeability through a process that may effect cadherins localized at the adherens junctions of endothelial cells. We examined the effects of T and PMA on cadherin immunoprecipitation using extracts of lung and heart from Gallus domesticus. We used SDS-PAGE and Western Blot analysis utilizing an anti-PAN cadherin detected by an AP-conjugated second antibody to detect a distinct band at 130 kDa. Lung and heart showed increased immunoprecipitation in this band after PMA and T as compared to control tissues. We suggest that PMA and T activate protein kinase C, through as yet undetermined mechanisms, to cause the
increased expression of endothelial cadherins.
Impacts
(N/A)
Publications
- WEIDNER, W.J., WADDELL, D. S., MILES, M.S. and HAGGERTY, K. 1997. Increased cadherin immunoprecipitation induced by phorbol myristate acetate (PMA) and thrombin (T) in avian lung and heart. The FASEB Journal (in press).
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