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Leukocyte function-associated antigen-1 deficiency impairs responses to polymicrobial sepsis

World Journal of Clinical Cases 2015年第9期3卷 793-806页

作者： Jia-Ren Liu Xiaohui Han Sulpicio G Soriano Koichi Yuki Department of Anesthesiology Perioperative and Pain MedicineBoston Children’s Hospital Department of Anaesthesia Harvard Medical School

AIM: To determine the role of leukocyte functionassociated antigen-1(LFA-1) in polymicrobial sepsis model in ***: Cecal ligation and puncture model was used to study polymicrobial sepsis in wild type and LFA-1 knockout(KO)(= CD11 a KO) mice. Their survivals were examined. Neutrophil recruitment to the abdominal cavity, bacterial tissue load and bacterial killing by neutrophils, tissue cytokine profiles, and serum cytokines were examined. Apoptosis of tissues was assessed using cleaved-caspase 3 and TUNNEL staining. The recruitment of neutrophils to various tissues was assessed using myeloperoxidase staining or measuring myeloperoxidase activity. RESULTS: LFA-1 deficiency significantly decreased survival(P = 0.0024) with the reduction of neutrophil recruitment to the abdominal cavity and higher bacterial load in blood. It was also associated with increased apoptosis in spleen and more organ injuries probed by interleukin-6 m RNA level. However, the deficiency of LFA-1 did not prevent neutrophil recruitment to lung, liver, spleen or kidney, which suggested the existence of LFA-1 independent recruitment mechanism in these organs. CONCLUSION: LFA-1 deficiency did not attenuate neutrophil recruitment to various organs to adequately mitigate secondary tissue injury in sepsis. It was associated with decreased neutrophil recruitment to the abdominal cavity, higher bacterial load, leading to increased mortality in an abdominal, polymicrobial sepsis.

关键词： Leukocyte function-associated antigen-1 Tissue injury Neutrophil recruitment Polymicrobial sepsis Apoptosis

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