Evidence for the involvement of a macrophage-derived chemotactic mediator in the neutrophil recruitment induced by staphylococcal enterotoxin B in mice.
Staphylococcus aureus secretes enterotoxins which are superantigens and the major cause of food poisoning in man. Staphylococcal enterotoxins types A and B can induce neutrophil migration into the peritoneal cavity of mice through sensory C-fiber neuropeptides, lipoxygenase or cyclooxygenase metabolites, nitric oxide, histamine, platelet-activating factor and resident macrophages. In this work, we examined the influence of macrophage-derived products on neutrophil migration during peritonitis induced by staphylococcal enterotoxin type B (SEB) in mice. Macrophages stimulated with SEB released a thermolabile neutrophil chemotactic protein with a molecular weight of 1,000-3,000 (by ultrafiltration). This release was inhibited 30% by dexamethasone (an inhibitor of cytokine synthesis and phospholipase A(2) activity), but not by indomethacin (a cyclooxygenase inhibitor) or BW755C (a dual cyclo- and lipoxygenase inhibitor). Dexamethasone also inhibited (100%) the neutrophil migration induced by the chemotactic protein. Similar inhibition occurred in mice pretreated with BWA4C (lipoxygenase inhibitor; 90%), BW755C (99%), BN52021 (platelet-activating factor-acether receptor antagonist; 93%), cimetidine (histamine H(2) receptor antagonist; 76%), capsaicin (a depletor of sensory C-fiber neuropeptides; 82%) and the neurokinin-1 receptor antagonist SR140333 (71%), but not by indomethacin or the neurokinin(2) receptor antagonist SR48968. These results confirm that macrophages are involved in the neutrophil recruitment induced by SEB, and that the chemotactic protein apparently induces neutrophil migration by a mechanism mediated by platelet-activating factor, histamine H(2) receptors, lipoxygenase products and substance P.
Desouza
Ivani A
IA
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, P.O. Box 6111, CEP 13083-970 Campinas, SP, Brazil. ivanidesouza@uol.com.br
Hyslop
Stephen
S
Franco-Penteado
Carla F
CF
Ribeiro-DaSilva
Glaci
G
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D002211:Capsaicin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D002927:Cimetidine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004224:Diterpenes; D004768:Enterotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D046934:Ginkgolides; D006877:Hydroxamic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D016209:Interleukin-8 / Q000502:physiology*; D007783:Lactones / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D044482:Benzeneacetamides; D004224:Diterpenes; D004768:Enterotoxins; D004791:Enzyme Inhibitors; D046934:Ginkgolides; D006877:Hydroxamic Acids; D016209:Interleukin-8; D007783:Lactones; D010880:Piperidines; D011812:Quinuclidines; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; C085215:SR 140333; C031818:enterotoxin B, staphylococcal; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003907:Dexamethasone; D002927:Cimetidine; C045856:ginkgolide B; D002211:Capsaicin; D007213:Indomethacin