Role of inducible nitric oxide synthase in leukocyte extravasation in vivo

Several recent studies have suggested that nitric oxide (NO) derived from t he inducible isoform of NO synthase (NOS) may act as an endogenous modulato r of the inflammatory response by inhibiting adhesion of leukocytes to endo thelial cells in vitro. Few studies have addressed specifically the role of iNOS in regulating leukocyte recruitment in vivo in a model of acute infla mmation. Thus, the objective of this study was to assess the role of iNOS i n modulating neutrophil (PMN) extravasation in an oyster glycogen-induced m odel of acute peritonitis in rats. Data obtained in the present study demon strates that injection (IP) of oyster glycogen induces massive and selectiv e PMN recruitment into the peritoneal cavity of rats at 6 hrs following OG administration. These extravasated cells were found to contain significant amounts of iNOS protein as assessed by Western blot analysis. Treatment of rats with the selective iNOS inhibitor L-iminoethyl-lysine (L-NIL) dramatic ally reduced NO levels in lavage fluid as measured by de. creases in nitrat e and nitrite concentrations without significantly affecting iNOS protein l evels. Although L-NIL inhibited NO production by >70%, it did not alter oys ter glycogen-induced PMN recruitment when compared to vehicle-treated rats. We conclude that PMN-associated, iNOS-derived NO does not play an importan t role in modulating extravasation of these leukocytes in this model of acu te inflammation. (C) 1999 Academic Press.