The role of macrophage 1 antigen in polymicrobial sepsis.

Macrophage 1 antigen (Mac-1, CD11bCD18) is a leukocyte adhesion molecule that is involved in many functions including leukocyte recruitment, phagocytosis, and neutrophil apoptosis. The previous report of mild polymicrobial, abdominal sepsis showed that the administration of anti-CD11b-blocking antibody administration attenuated lung injury without any survival benefit. Here we tested the impact of Mac-1 deficiency in severe polymicrobial abdominal sepsis model. Polymicrobial sepsis was studied using cecal ligation and puncture model in wild-type (WT) or Mac-1-deficient (CD11b knockout [KO]) mice, and their outcomes were examined. Bacterial tissue load and the recruitment of neutrophils to the abdominal cavity were assessed. In vitro bacterial killing assay was performed. Serum cytokine levels were measured using multiarray. Apoptosis of spleen tissues was assessed using Western blot analysis and immunohistochemistry (cleaved caspase 3 and TUNEL staining). In addition, in vitro apoptosis assay was performed using primary splenocytes from both WT and KO mice. The recruitment of neutrophils to lung was assessed by measuring myeloperoxidase activity. Macrophage 1 antigen deficiency significantly decreased survival (survival percentage WT 43.5% vs. KO 13.0%; P = 0.0038) with higher bacterial load in blood and more severe systemic inflammation. Knockout mice demonstrated higher apoptosis both in vivo and in vitro. The recruitment of neutrophils to lung was not different between WT and KO mice. Macrophage 1 antigen deficiency was associated with poorer outcomes, more bacterial load, systemic inflammation, and splenic apoptosis. However, Mac-1 deficiency did not attenuate neutrophil recruitment to lung.