Document Detail


LFA-1 and MAC-1 mediate pulmonary recruitment of neutrophils and tissue damage in abdominal sepsis.
MedLine Citation:
PMID:  18197144     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neutrophil-mediated lung damage is an insidious feature in septic patients, although the adhesive mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of the present study was to define the role of lymphocyte function antigen-1 (LFA-1) and membrane-activated complex 1 (Mac-1) in septic lung injury. Pulmonary edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, and CXC chemokines were determined after cecal ligation and puncture (CLP). Mice were treated with monoclonal antibodies directed against LFA-1 and Mac-1 before CLP induction. Cecal ligation and puncture induced clear-cut pulmonary damage characterized by edema formation, neutrophil infiltration, and increased levels of CXC chemokines in the lung. Notably, immunoneutralization of LFA-1 or Mac-1 decreased CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 64%. Moreover, functional inhibition of LFA-1 and Mac-1 abolished CLP-induced lung damage and edema. However, formation of CXC chemokines in the lung was intact in mice pretreated with the anti-LFA-1 and anti-Mac-1 antibodies. Our data demonstrate that both LFA-1 and Mac-1 regulate pulmonary infiltration of neutrophils and lung edema associated with abdominal sepsis. Thus, these novel findings suggest that LFA-1 or Mac-1 may serve as targets to protect against lung injury in polymicrobial sepsis.
Authors:
Muhammad Asaduzzaman; Su Zhang; Shahram Lavasani; Yusheng Wang; Henrik Thorlacius
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  30     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-02     Completed Date:  2008-12-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  254-9     Citation Subset:  IM    
Affiliation:
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemokines / metabolism*
Edema / immunology
Gene Expression Regulation*
Humans
Leukocytes / microbiology
Lung / immunology,  metabolism*
Lung Injury
Lymphocyte Function-Associated Antigen-1 / biosynthesis*
Macrophage-1 Antigen / biosynthesis*
Male
Mice
Mice, Inbred C57BL
Models, Biological
Neutrophils / immunology,  metabolism*
Sepsis / blood*,  metabolism
Chemical
Reg. No./Substance:
0/Chemokines; 0/Lymphocyte Function-Associated Antigen-1; 0/Macrophage-1 Antigen

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