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Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells
Author(s) -
Kubes Paul,
Kanwar Samina,
Niu XiaoFei,
Gaboury Jeffrey P.
Publication year - 1993
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.7.13.8405815
Subject(s) - nitric oxide , degranulation , superoxide , mast cell , chemistry , superoxide dismutase , cell adhesion , xanthine oxidase , microbiology and biotechnology , biochemistry , immunology , biology , cell , oxidative stress , enzyme , receptor , organic chemistry
Recent work has demonstrated that inhibition of nitric oxide production with various nitric oxide synthesis inhibitors ( l ‐NAME, l ‐NMMA) initiate leukocyte adhesion to postcapillary venules. The objective of this study was to elucidate the mechanism (or mechanisms) that promote the l ‐NAME‐induced leukocyte response. Intravital microscopy was used to examine 25–40 μ m venules in the rat mesentery. Nitric oxide synthesis was inhibited with l ‐NAME and leukocyte adhesion was observed over the first 60 min. The fourfold increase in leukocyte adhesion was independent of alterations in venular red blood cell velocity. The adhesion was superoxide‐mediated inasmuch as superoxide dismutase (SOD) abolished the rise in leukocyte adhesion associated with nitric oxide synthesis inhibition. Ketotifen, a mast cell stabilizer, also abolished the rise in leukocyte adhesion induced by l ‐NAME, Histology revealed that mast cell degranulation occurred only in animals treated with l ‐NAME but not in animals pretreated with SOD or kctotifen. This observation suggests that mast cells become activated in the absence of nitric oxide production and superoxide contributes to the mast cell activation. The l ‐NAME‐induced leukocyte adhesion could be reproduced by infusing hypoxanthine/xanthine oxidase (a superoxide generating system) or compound 48/80 (an activator of mast cells) and both responses were attenuated by ketotifen. These data suggest that inhibition of nitric oxide synthesis results in a superoxide and mast cell‐dependent leukocyte adhesion.—Kubes, P., Kanwar, S., Niu, X.‐F., Gaboury, J. P. Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. FASEB J. 7: 1293‐1299; 1993.