Role of inducible nitric oxide synthase in leukocyte extravasation in vivo.
Several recent studies have suggested that nitric oxide (NO) derived from the inducible isoform of NO synthase (NOS) may act as an endogenous modulator of the inflammatory response by inhibiting adhesion of leukocytes to endothelial cells in vitro. Few studies have addressed specifically the role of iNOS in regulating leukocyte recruitment in vivo in a model of acute inflammation. Thus, the objective of this study was to assess the role of iNOS in modulating neutrophil (PMN) extravasation in an oyster glycogen-induced model of acute peritonitis in rats. Data obtained in the present study demonstrates that injection (IP) of oyster glycogen induces massive and selective 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) dramatically reduced NO levels in lavage fluid as measured by decreases in nitrate and nitrite concentrations without significantly affecting iNOS protein levels. Although L-NIL inhibited NO production by >70%, it did not alter oyster glycogen-induced PMN recruitment when compared to vehicle-treated rats. We conclude that PMN-associated, iNOS-derived NO does not play an important role in modulating extravasation of these leukocytes in this model of acute inflammation.
Cockrell
A
A
Department of Molecular and Cellular Physiology, LSU Medical Center, Shreveport, Louisiana, 71130, USA.
Laroux
F S
FS
Jourd'heuil
D
D
Kawachi
S
S
Gray
L
L
Van der Heyde
H
H
Grisham
M B
MB
D000208:Acute Disease; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006003:Glycogen / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010125:Ostreidae; D010538:Peritonitis / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew
C090663:N(6)-(1-iminoethyl)lysine; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D006003:Glycogen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008239:Lysine