The primary goal of this investigation is to elucidate the role of a tissue elastase, presumably synthesized by fibroblasts or smooth muscle cells, on the normal and pathological degradation of connective tissues. For the first phase of these studies, it is essential to use a tissue, that under normal conditions is rapidly synthesizing and degrading elastin. The system we will use is the pregnant rat uterus, which synthesizes and turns over greater than five times the initial elastin content of the uterus within a twenty day period. We will purify the elastase responsible for the elastolysis and make antibodies to it. For comparative purposes, rat pancreatic and leukocyte elastase will also be purified and antibodies made to coacervated Alpha-elastin. Radioimmunoassays, in combination with immunostaining techniques, will enable us to show the chronological sequence of synthesis and secretion of the elastin and elastase, and which cell type is responsible for their production. In the second phase of this investigation, we will use these same antibodies to study elastase and elastin production by the rat lung. Under conditions of lung injury (NO2, cigarette smoke or bleomycin) what cells in the lung are involved in the development of the lesions that evolve? Do the lung cells release their own elastase and is this a major contributor to lung elastin degeneration, relative to leukocyte elastase?
| Ottlecz, A; Walker, S; Conrad, M et al. (1991) Neutral metalloendopeptidase associated with the smooth muscle cells of pregnant rat uterus. J Cell Biochem 45:401-11 |
| Percival, S; Starcher, B (1988) Identification of a uterine elastase in the pregnant rat uterus. Proc Soc Exp Biol Med 189:117-29 |
