The objective of this proposal is to obtain a better understanding of the mechanisms controlling fibrosis in the adult human lung. Using techniques of tissue culture and collagen biochemistry I will characterize the factors that control fibroblaslt growth and biosynthesis in normals, patients with sarcoidosis, and patients with a variety of fibrotic and non-fibrotic lung diseases. The proposal has 4 major goals. (A) Further definition of the biology of the normal llunlg fibroblast. This will include characterizing the effect on fibroblast growth and biosynthesis of lung and blood mononuclear cells, lullg and blood mononuclear cell subpopulations, prostaglandins, corticosteroids, lymphocyte growth factors (Interleuken-I & II), and immunoregulatory serum factors. Mononuclear cell factors that modulate fibroblast function will be partially characterized. (B) Characterization of the processes (normal and abnormal) that modulate fibroblast growth and biosynthesis in sarcoidosis. This will be done by detailing the effect on fibroblast growth and biosynthesis of the serum, lunng and blood mononuclear cells, and lulng and blood mononuclear cell subpopulations of patients with sarcoidosis. (C) Determination if in vitro phenomina (pattern of modulation of fibroblast function, spontaneous production of lymphocyte growht factors) correlate with disease activity, disease progression, or the development of pulmonary fibrosis in sarcoidosis. This will be done by correlating the course of a patients disease (assessed clinically, functionally, immunologically, and enzymatically) with serially preformed in vitro studies. (D) Characterization of the spectrum of phenotypic heterogeneity of fibroblasts from normal and fibrotic lungs. This will be done by determining the basal rates of growth and biosynthesis of cells to mononuclear cell, prostaglandin, and corticoseroid modulation of fibroblast function will be examined.
Showing the most recent 10 out of 18 publications
