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 α (TNF-α), interleukin 1β (IL-1β) 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.