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

作　　者：Jia-Ren Liu Xiaohui Han Sulpicio G Soriano Koichi Yuki 

机构地区：[1]Department of Anesthesiology,Perioperative and Pain Medicine,Boston Children’s Hospital [2]Department of Anaesthesia,Harvard Medical School

出　　处：《World Journal of Clinical Cases》2015年第9期793-806,共14页世界临床病例杂志

基　　金：Supported by CHMC Anesthesia Foundation(Soriano SG and Yuki K);William F.Milton Fund(Yuki K);BCH Endowed Chair in Pediatric Neuroanesthesia(Soriano SG)

摘　　要：AIM: To determine the role of leukocyte functionassociated antigen-1(LFA-1) in polymicrobial sepsis model in mice.METHODS: 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.AIM: To determine the role of leukocyte functionassociated antigen-1(LFA-1) in polymicrobial sepsis model in mice.METHODS: 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 

分 类 号：R515.3[医药卫生—内科学]