In our previous studies (NICHD R01 19002 we found that macrophages recruited by surgical injury to enter the peritoneal cavity secreted substances critical to post surgical peritoneal repair. We observed that supernatants, obtained from short-term cultures of normal rabbit (nonsurgical or resident) peritoneal macrophages, contain material which modulates fibroblast proliferation, as well as secretion of connective tissue proteins (collagen, glycosaminoglycans). Macrophages removed from the peritoneal cavity of rabbits after surgery contain an increased respiratory burst, and secretion of a substance which induces fibroblast proliferation. The preexposure of post-surgical macrophages to cyclohexamide in vitro eliminates or markedly reduces the secretion of these activities in situ or in spent protein synthesis and secretion. It was not clear from these initial observations, however, whether peritoneal macrophage culture supernatants contained one or several active principles. Nor was it clear whether these studies detected a previously unknown substance or whether they were simply describing new functional properties for previously identified macrophage secretory products, such as Interleukin 1, MDGF etc. The purpose of this grant is to address these issues. In addition to obtaining further insight into the functions of post-surgical peritoneal macrophages, the studies outline here are designed to provide further understanding of the role this post-surgical macrophage plays in peritoneal healing and adhesion formation. Accordingly, the specific aims of this projects are: 1) to characterize macrophages present at the site of post-surgical trauma, utilizing those parameters traditionally used to define macrophage activation including superoxide radical production and tumoricidal activity. 2) to examine the secretory capabilities of macrophages from post-surgical sites, in particular the production of neutral proteases, and arahodonic acid metabolites. 3) to characterize ascitic fluids from post-surgical peritoneum for the level of neutral proteases, protease inhibitors and macrophage activity factors, 4) to examine the role of macrophages in the preparation of fibroblasts for tissue repair and secretion of proteins necessary for matrix formation.
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