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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019002-06
Application #
3316154
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-07-01
Project End
1990-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Los Angeles County-University of S Cal Medical Center
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
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Fukasawa, M; Bryant, S M; diZerega, G S (1988) Superoxide anion production by postsurgical macrophages. J Surg Res 45:382-8
Greenwald, D; Nakamura, R; diZerega, G (1988) Determination of pH and pKa in human peritoneal fluid. Curr Surg 45:217-8
Shimanuki, T; Nishimura, K; Montz, F J et al. (1987) Localized prevention of postsurgical adhesion formation and reformation with oxidized regenerated cellulose. J Biomed Mater Res 21:173-85
Fukasawa, M; Bryant, S M; Nakamura, R M et al. (1987) Modulation of fibroblast proliferation by postsurgical macrophages. J Surg Res 43:513-20
Orita, H; Campeau, J D; Nakamura, R M et al. (1986) Modulation of fibroblast proliferation and transformation by activated macrophages during postoperative peritoneal reepithelialization. Am J Obstet Gynecol 155:905-11
Shimanuki, T; Nakamura, R M; diZerega, G S (1986) A kinetic analysis of peritoneal fluid cytology and arachidonic acid metabolism after abrasion and reabrasion of rabbit peritoneum. J Surg Res 41:245-51
Orita, H; Campeau, J D; Gale, J A et al. (1986) Differential secretion of plasminogen activator activity by postsurgical activated macrophages. J Surg Res 41:569-73
Shimanuki, T; Nakamura, R M; diZerega, G S (1985) In vivo modulation of leukotaxis by non-steroidal anti-inflammatory drugs. Agents Actions 17:80-3
Montz, F J; diZerega, G S (1985) Genital tuberculosis in an elderly woman with the primary symptoms of pelvic prolapse: case report. Am J Obstet Gynecol 152:42-3

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