Nitric oxide regulates the aggregation of stimulated human neutrophils.
Neutrophil aggregation is mediated by both CD18 integrin and L-selectin. Nitric oxide attenuates the integrin-mediated adhesion of neutrophils to collagen and to endothelium and may therefore affect aggregation as well. FMLP-stimulated neutrophils exposed to l-arginine showed increased and prolonged aggregation, whereas cells pretreated with L-NAME did not differ from FMLP-stimulated controls. Nitric oxide is known to induce ADP ribosylation of G-actin, which inhibits polymerization. We detected equivalent levels of total F-actin in cells pretreated with l-arginine or L-NAME and non-pretreated controls. However, neutrophils pretreated with l-arginine and stimulated by CD18 integrin cross-linking exhibited a more limited increase in total F-actin, compared to control and L-NAME-pretreated cells. Thus at least two signaling pathways may be involved FMLP-stimulated aggregation, mediated by CD18 integrins. More specifically, it is plausible that FMLP-receptor signaling upregulates CD18 integrins and endogenous NO subsequently modulates CD18-mediated signaling to prolong aggregation, possibly through ADP-ribosylation of actin.
Department of Medical Microbiology, University of Linköping, Linköping, SE-581 85, Sweden.
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Forslund
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Nilsson
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Sundqvist
D000199:Actins / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D018821:CD18 Antigens / Q000187:drug effects / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D000906:Antibodies; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D019041:L-Selectin; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001120:Arginine; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester