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Modulation of human neutrophil inflammatory responses by nitric oxide: studies in unprimed and LPS‐primed cells
Author(s) -
Nath Jayasree,
Powledge Annette
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.62.6.805
Subject(s) - nitric oxide , lipopolysaccharide , n formylmethionine leucyl phenylalanine , superoxide , exocytosis , granulocyte , biology , priming (agriculture) , sodium nitroprusside , intracellular , neutrophile , immunology , biochemistry , microbiology and biotechnology , inflammation , enzyme , endocrinology , secretion , botany , germination
Because nitric oxide (NO) can act both as a regulatory and as a toxic molecule, we have studied N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLF) ‐stimulated responses of human neutrophils (PMNs) during various conditions of NO modulation in unprimed and bacterial lipopolysaccharide (LPS) ‐primed cells. Effects of various NO modulators were assessed on stimulated superoxide (O 2 ‐ ) generation, granule exocytosis, homotypic aggregation, and rises in intracellular free Ca 2+ ([Ca 2+ ] i ). Significant differences in the effects of various NO modulators on inflammatory responses of PMNs kept in stirred suspension versus those kept under static and/or adherent conditions, were observed. L‐arginine, the physiological substrate for NO synthase (NOS), and N G ‐nitro‐L‐arginine methyl ester, an inhibitor of NOS, both caused a 40‐50% inhibition of LPS‐induced priming of O 2 ‐ generation in PMNs in stirred suspension, but not in LPS‐primed PMNs under static or adherent conditions. The NO donors, sodium nitroprusside and S ‐nitroso‐ N ‐acetylpenicillamine, completely abrogated the LPS‐induced priming of 0 2 ‐ generation in PMNs in suspension, while causing only a 40‐50% inhibition in PMNs under static or adherent conditions. The Ca 2+ ionophore, A23187, prevented the LPS‐induced priming of 0 2 ‐ generation without affecting 0 2 ‐ generation in unprimed PMNs. LPS priming of PMNs induced about a twofold increase in fMLF‐stimulated homotypic aggregation, exocytosis of secondary granules, and rises in [Ca 2+ ] i . In related studies, we also provide definitive evidence for enzymatic formation of NO in human PMNs and demonstrate a significant decrease in NO levels in LPS‐primed PMNs. Taken together, these findings indicate that NO modulates PMN inflammatory responses and plays a protective role in priming and activation processes of inflammatory PMNs. J. Leukoc. Biol . 62: 805–816; 1997.