Role of blood- and tissue-associated inducible nitric-oxide synthase in colonic inflammation.
There is evidence that inducible nitric-oxide synthase (iNOS)-derived NO contributes to the pathophysiology of intestinal inflammation. The aims of this study were to assess the role of iNOS in the development of dextran sodium sulfate (DSS)-induced colonic inflammation and to define the contribution of tissue-specific iNOS expression to this inflammatory response. Study groups included: 1) wild-type (WT) mice; 2) WT=>WT bone marrow chimeras with normal iNOS function; 3) WT=>iNOS-/- chimeras (with functional blood cell iNOS, but iNOS-deficient tissue); 4) iNOS-/-=>WT chimeras (with iNOS-deficient blood cells, but normal tissue iNOS activity); and 5) iNOS-deficient mice. In WT mice and WT=>WT chimeras, DSS-induced colonic inflammation was characterized by bloody diarrhea and a high disease activity index. However, WT=>iNOS-/- and iNOS-/-=>WT chimeras and iNOS-/- mice exhibited an attenuated disease activity index, with parallel changes in histopathology. Colonic myeloperoxidase (MPO) was comparably elevated in DSS-treated WT mice (30.1+/-1.7) and WT=>WT chimeras (29.0+/-1), whereas MPO was significantly reduced in iNOS-/- mice and iNOS-/-=>WT chimeras (9.5+/-1.7 and 15.6+/-2.2, respectively). WT=>iNOS-/- chimeras exhibited the lowest MPO activity (3.7+/-0.6). Our findings implicate both blood cell- and tissue-derived iNOS in DSS-induced colonic inflammation, with tissue-associated iNOS making a larger contribution to the recruitment of inflammatory cells.
Krieglstein
Christian F
CF
Department of General Surgery, Westfalian Wilhelm's University, Muenster, Germany.
Anthoni
Christoph
C
Cerwinka
Wolfgang H
WH
Stokes
Karen Y
KY
Russell
Janice
J
Grisham
Matthew B
MB
Granger
D Neil
DN
D000818:Animals; D016026:Bone Marrow Transplantation; D001947:Breeding; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D003106:Colon / Q000201:enzymology*; D016264:Dextran Sulfate / Q000633:toxicity; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D009928:Organ Specificity; D009195:Peroxidase / Q000378:metabolism; D018183:Transplantation Chimera / Q000378:metabolism
D016264:Dextran Sulfate; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II