Effect of mast cells depletion on the failure of neutrophil migration during sepsis.
The possible role of mast cell in neutrophil migration failure during sepsis was examined in a polymicrobial sepsis model in mice. Mast cells were depleted by compound 48/80 or lysed by distilled water, both preventing the neutrophil migration failure. This phenomenon was accompanied by reduction of bacteria in the peritoneal cavity and blood, serum tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and nitrate (NO3) and by an increase in mice survival rate. Neither neutrophil migration failure nor significant mortality was observed when lethal inoculum was injected into the air-pouch model, a cavity poorly populated by mast cells. Confirming that neutrophil migration failure is a phenomenon induced by systemic circulating mediators, it was observed that i.p. administration of lethal inoculum induced a neutrophil migration failure to the air pouch inoculated with non-lethal bacterial challenge. These results suggest that mast cells have a key role in the genesis of neutrophil migration failure, and, consequently, contribute to the systemic inflammatory response and mortality in severe sepsis.
Carvalho
Michel
M
Department of Pharmacology, Faculty of Medicine Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Benjamim
Cláudia
C
Santos
Fabrício
F
Ferreira
Sérgio
S
Cunha
Fernando
F
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D015169:Colony Count, Microbial; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D007375:Interleukin-1; D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D003189:p-Methoxy-N-methylphenethylamine