This grant renewal is an extension of our studies on the structural determinants of vascular permeability in the lung. The long-range objective is to identify the components of the tight and adhering junctions which regulate the permeability barrier in the pulmonary endothelium. Although proteins specific for the two types of endothelial junctions have been recently identified, no information currently exists regarding their distribution in different segments of the pulmonary vasculature and their relationship to structure and function of the endothelial permeability barrier. Using colloidal gold techniques and antibodies, which recognize ZO-1 and Plakoglobin, two junction-specific proteins, we will determine, by morphometry and immuno electron microscopy, the distribution of these components of the endothelial junctional complex in various segments of the rat pulmonary vascular system. In a rat model of H202-induced pulmonary edema we will correlate increased endothelial permeability with selective loss of junctional components as detected by immuno electron microscopy and freeze-fracture techniques. These studies are expected to provide new insight in the pathogenesis of a variety of human pulmonary diseases such as the Adult Respiratory Distress Syndrome (ARDS), oxygen toxicity and ischemia-reperfusion injury in which oxygen derivatives and H202 in particular, are released by activated neutrophiles or endothelial cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032482-11
Application #
2217032
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1984-08-01
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pietra, G G; Johns, L W (1996) Confocal- and electron-microscopic localization of FITC-albumin in H2O2-induced pulmonary edema. J Appl Physiol 80:182-90
Pietra, G G (1994) Histopathology of primary pulmonary hypertension. Chest 105:2S-6S
Salhany, K E; Pietra, G G (1993) Extranodal lymphoid disorders. Am J Clin Pathol 99:472-85
Pietra, G G (1991) Pathologic mechanisms of drug-induced lung disorders. J Thorac Imaging 6:1-7
Dessy, E; Pietra, G G (1991) Pseudomesotheliomatous carcinoma of the lung. An immunohistochemical and ultrastructural study of three cases. Cancer 68:1747-53
Pietra, G G (1990) The pathology of carcinoma of the lung. Semin Roentgenol 25:25-33
Pietra, G G; Johns, L (1990) Leaky intra-acinar arteries in rat lungs perfused with hydrogen peroxide. J Appl Physiol 69:1110-6
Kapanci, Y; Burgan, S; Pietra, G G et al. (1990) Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension. Am J Pathol 136:881-9
Palevsky, H I; Pietra, G G; Fishman, A P (1990) Pulmonary veno-occlusive disease and its response to vasodilator agents. Am Rev Respir Dis 142:426-9
Barrett, T E; Pietra, G G; Maycock, R L et al. (1989) Acrylic resin pneumoconiosis: report of a case in a dental student. Am Rev Respir Dis 139:841-3

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