and Specific Aims.) Interstitial pulmonary fibrosis is characterized by alterations in the lung parenchyma with increased fibroblast numbers, excess connective tissue and increased rate of matrix synthesis. The mechanisms responsible for these tissue alterations are poorly understood. Fibroblasts are the major cell type responsible for normal connective tissue turnover and accumulation of matrix elements in fibrosis. Cytokines, growth factors, complement proteins and other inflammatory mediators have been implicated in the pathogenesis of fibrosis in man. Evidence indicates that human lung fibroblasts are heterogeneous and subpopulations interact differently with inflammatory mediators. The application proposes to utilize antibodies and cDNAs for the two C1q receptors to identify fibroblast subpopulations in normal adult and fibrotic human lungs.
The Specific Aims are: 1) to produce antibodies against human lung fibroblast receptors for collagen- and globular- domains of the C1q molecule and determine their specificity to human lung fibroblast subpopulations; 2) to isolate from human lung fibroblasts cDNAs coding for the receptors for collagen- and globular-domains of C1q molecule and assess differential expression of these receptors in two human lung fibroblast subpopulations; 3) to study the regulation of C1q receptors by cytokines in human lung fibroblasts and determine whether synthesis of these receptors is related to type I collagen gene expression; 4) to identify fibroblast subpopulations with differential C1q receptors and collagen synthesis in normal and fibrotic human lungs using antibodies and cDNA probes. From these experiments, the role of fibroblasts with different C1q receptors and the role of fibroblast heterogeneity in idiopathic pulmonary fibrosis (IPF) may be determined. The results may also help to identify potential marker(s) for early detection of fibrosis and may aid in interventional studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039854-07
Application #
2219400
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1987-09-30
Project End
1998-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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