Elucidation of the early events contributing to zymosan-induced multiple organ dysfunction syndrome using MIP-1 alpha, c3 knockout, and C5-deficient mice

Using a zymosan-induced mouse model of multiple organ dysfunction syndrome (MODS), it has been shown that the absence of MIP-1 alpha increased mortali ty fourfold, whereas the absence of C5 decreased mortality fourfold. The pu rpose of the present study was to determine the early events following zymo san injection in MIP-1 alpha knockout and C5-deficient mice. B10.D2/nSnJ (C 5-sufficient) and B10.D2/0SnJ (C5-deficient) and genetically matched MIP-1 alpha +/+ and MIP-1 alpha -/- mice were divided into 3 groups: Group1 recei ved no injection, Group 2 received intraperitoneal saline injection (1.0 mt ), and Group 3 were given intraperitoneal zymosan (1mg/gm, 1.0 mt). Two hou rs, 24 h, and 48 h after injection, peritoneal exudate leukocyte counts, to tal WBC count, lung MPO levels, and organ histology were examined for signs of changes in cellular infiltration. An acute local and systemic inflammat ory response characterized by an increase in the peritoneal leukocyte count , total WBC counts, and circulating neutrophil levels was observed within 2 -48 h of zymosan injection. Lack of MIP-1 alpha attenuated local recruitmen t of phagocytes into the peritoneal cavity, and absence of MIP-1 alpha or C 5 caused a decrease in circulating neutrophil levels. The presence or absen ce of either C5 or MIP-1 alpha did not affect early pulmonary neutrophil se questration. Organ histopathology suggested early neutrophil infiltration i n the lung and spleen within 48 h. These studies indicate that MIP-1 alpha and C5 play a critical role in modulating cellular changes associated with lethality in a zymosan model of MODS.