Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 16, 2015; 3(9): 793-806
Published online Sep 16, 2015. doi: 10.12998/wjcc.v3.i9.793
Leukocyte function-associated antigen-1 deficiency impairs responses to polymicrobial sepsis
Jia-Ren Liu, Xiaohui Han, Sulpicio G Soriano, Koichi Yuki
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
Jia-Ren Liu, Xiaohui Han, Sulpicio G Soriano, Koichi Yuki, Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, United States
Author contributions: All the authors contributed to this paper.
Supported by CHMC Anesthesia Foundation (Soriano SG and Yuki K), William F. Milton Fund (Yuki K); and BCH Endowed Chair in Pediatric Neuroanesthesia (Soriano SG).
Institutional review board statement: The study was reviewed and approved by Boston Children’s Hospital Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Boston Children’s Hospital (protocol number 2218/2893).
Conflict-of-interest statement: None.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Koichi Yuki, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, United States. koichi.yuki@childrens.harvard.edu
Telephone: +1-617-3556225 Fax: +1-617-7300894
Received: January 24, 2015
Peer-review started: February 1, 2015
First decision: March 6, 2015
Revised: April 10, 2015
Accepted: June 15, 2015
Article in press: June 16, 2015
Published online: September 16, 2015
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.

Keywords: Leukocyte function-associated antigen-1, Tissue injury, Neutrophil recruitment, Polymicrobial sepsis, Apoptosis

Core tip: We report our result on the role of leukocyte function-associated antigen-1 (LFA-1) in polymicrobial abdominal sepsis model induced by cecal ligation and puncture. LFA-1 is a key player in neutrophil migration, but its role in neutrophil migration to tissues in polymicrobial sepsis is yet to be determined. This study demonstrated that LFA-1 deficiency blocked neutrophil migration to the abdominal cavity, but maintained migration to other organs, and reduced survival in sepsis.