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Regulation of macrophage phagocytosis of apoptotic neutrophils by adhesion to fibronectin.
Author(s) -
McCutcheon Judith C.,
Hart Simon P.,
Canning Mary,
Ross Katherine,
Humphries Martin J,
Dransfield Ian
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.5.600
Subject(s) - phagocytosis , fibronectin , macrophage , inflammation , biology , microbiology and biotechnology , integrin , apoptosis , receptor , immunology , extracellular matrix , biochemistry , in vitro
The potential for leukocyte‐mediated host tissue damage during resolution of inflammatory responses is influenced by the rate at which extravasated apoptotic leukocytes are cleared from inflammatory sites. Regulation of macrophage capacity for clearance of apoptotic granulocytes is likely to be an important factor determining whether inflammation ultimately resolves or progresses to a chronic state. In this study we have investigated the molecular basis for rapid augmentation of macrophage phagocytosis of apoptotic neutrophils, which was observed following macrophage adhesion to fibronectin. We used a combination of monoclonal antibodies, blocking peptides, and recombinant fibronectin fragments to investigate the role of β 1 integrins in mediating the fibronectin effects. Blockade of α 5 β 1 or α 4 β 1 alone did not attenuate fibronectin‐augmentation of phagocytosis. In addition, adhesion of macrophages to recombinant fibronectins lacking α 4 β 1 recognition motifs failed to promote phagocytosis of apoptotic neutrophils. Our results would be consistent with a model in which multiple fibronectin receptors, including β 1 integrins, act cooperatively to augment macrophage phagocytic responses. Together, these data suggest that the extracellular matrix environment of macrophages may provide regulatory signals that act indirectly to rapidly alter the potential for removal of apoptotic cells and influence the process of resolution of inflammation. J. Leukoc. Biol. 64: 600–607; 1998.