Premium
Release of preformed IL‐12 by the macrophage scavenger receptor MARCO
Author(s) -
Sulahian Timothy H.,
Kobzik Lester
Publication year - 2007
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.21.5.a183-d
Subject(s) - biotinylation , monoclonal antibody , internalization , scavenger receptor , innate immune system , cytokine , microbiology and biotechnology , phagocytosis , macrophage , chemistry , receptor , immune system , biology , immunology , antibody , biochemistry , in vitro , lipoprotein , cholesterol
Alveolar macrophages (AM) function to provide innate immune defense against inhaled pathogens and particles. The class A scavenger receptor MARCO is essential for optimal binding and clearance of unopsonized particles and bacteria by AMs. To analyze the role of MARCO in signaling for phagocytosis and cytokine responses, we developed a highly specific cross‐linking probe based on a biotinylated anti‐huMARCO monoclonal antibody coupled to biotinylated red blood cells (RBC) via a streptavidin bridge. Using human monocyte‐derived macrophages cultured to develop an AM‐like phenotype, we observed specific binding, but not internalization, of the MARCO‐targeted red cells. Cytokine release analysis showed robust and specific production of IL‐12 (p70, ~100 pg/ml), but not TNF‐alpha, after binding of MARCO‐targeted RBC by human macrophages. Furthermore, we found this release to be independent of IFN‐gamma priming and extremely rapid (< 10 min). In addition to its role in bacterial and particle binding, the MARCO receptor may also modify innate and adaptive lung immunity by triggering the release of this critical cytokine.