This proposal aims to define the contribution of the pulmonary microvascular endothelium to size and charge permselectivity in the lung. The hypothesis to be tested is that anionic glycoproteins in glycosaminoglycans on the surface of the plulmonary microvascular endothelium are organized in discrete domains which may influence the routes taken by macromolecules across the capillary wall. Pathways for neutral and charged macromolecules across the capillary walls will be identified qualitatively by electron microscopy using electron-dense permeability probes of different molecular size and net electrical charge. The experiments will be done in the isolated perfused rat lung preparation to avoid systemic effects resulting from interaction between charged probes and blood constituents. Quantitative assessment of transcapillary movement of permeability probes will be done by morphometric measurements at different time intervals and/or by measurements of lung radioactivity in lungs perfused with radioactive permeability probes. Selective enzymatic removal of glycoproteins or glycosaminoglycans on the endothelium will provide insights in the biochemical nature of the constituents of the charged barrier. Using lectins bound to colloidal gold the distribution of carbohydrate units of different glycoproteins on the microvascular endothelium and adjacent basement membrane will be examined in thin sections of lungs. The overall goal of the project is to identify new structural determinants of lung permeability and gain information for future studies on mechanism of endothelial damage in differnt types of lung injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL032482-04
Application #
3343822
Study Section
Pathology A Study Section (PTHA)
Project Start
1984-08-01
Project End
1992-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
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
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
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
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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