title: Leukocyte function-associated antigen-1 deficiency impairs responses to polymicrobial sepsis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Jia-Ren
authors.initials: JR
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Sulpicio G
authors.initials: SG
authors.lastname: Soriano
authors.affiliation: 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.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yuki
keywords: Apoptosis; Leukocyte function-associated antigen-1; Neutrophil recruitment; Polymicrobial sepsis; Tissue injury