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Role of macrophage scavenger receptor MARCO in lung innate defenses against influenza
Author(s) -
Ghosh Sanjukta,
Kobzik Lester
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.320.2
Subject(s) - scavenger receptor , bronchoalveolar lavage , chemokine , immunology , innate immune system , inflammation , influenza a virus , cxcl1 , alveolar macrophage , receptor , macrophage , lung , biology , virus , medicine , microbiology and biotechnology , immune system , in vitro , lipoprotein , biochemistry , cholesterol
The class A scavenger receptor MARCO is expressed by lung macrophages and mediates clearance of inhaled bacteria and particulate matter. We sought to investigate whether MARCO contributes to early innate defenses against another type of inhaled pathogen, the influenza virus. We compared the inflammatory response of normal or MARCO‐deficient mice following intranasal infection with H1N1 strain of influenza A virus A/PR8/34 (200pfu). At 24 and 48 hours after infection MARCO−/− mice showed 5–8 fold more neutrophils in the bronchoalveolar fluid (BALF) compared to WT controls. Concomitant with the increase in neutrophils, there was a >4‐fold increase in mRNA expression of the potent neutrophil chemoattractant molecule, CXCL1, in the MARCO−/− BALF cells. Analysis of gene expression in BALF cells 48 hours after infection revealed greater expression in MARCO −/− mice of several chemokines and cytokines including interferon‐gamma. Infected MARCO−/− mice also exhibited greater loss of body weight indicative of greater morbidity. These findings suggest that lung macrophages contribute to clearance of virus in the early phase of infection, and that the scavenger receptor MARCO mediates uptake of virus by alveolar macrophages, thereby reducing early injury and acute inflammation. NIEHS 11008, 00002.