Jia-Ren Liu1, Xiaohui Han1, Sulpicio G Soriano1, Koichi Yuki1. 1. Jia-Ren Liu, Xiaohui Han, Sulpicio G Soriano, Koichi Yuki, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, United States.
Abstract
AIM: To determine the role of leukocyte function-associated 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) (= CD11a 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 mRNA 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 function-associated 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) (= CD11a 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 mRNA 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.
Authors: Aras Kadioglu; Katia De Filippo; Mathieu Bangert; Vitor E Fernandes; Luke Richards; Kristian Jones; Peter W Andrew; Nancy Hogg Journal: J Immunol Date: 2011-04-01 Impact factor: 5.422
Authors: D C Anderson; F C Schmalsteig; M J Finegold; B J Hughes; R Rothlein; L J Miller; S Kohl; M F Tosi; R L Jacobs; T C Waldrop Journal: J Infect Dis Date: 1985-10 Impact factor: 5.226
Authors: William P Bailey; Kui Cui; Christopher L Ardell; Kasey R Keever; Sanjay Singh; Diego J Rodriguez-Gil; Tammy R Ozment; David L Williams; Valentin P Yakubenko Journal: J Leukoc Biol Date: 2021-01-13 Impact factor: 4.962