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Activation of CR3‐mediated phagocytosis by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3‐kinase, and protein kinase C ζ
Author(s) -
Lutz Michael A.,
Correll Pamela H.
Publication year - 2003
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 - 10.1189/jlb.0602319
Subject(s) - biology , microbiology and biotechnology , phagocytosis , receptor tyrosine kinase , tyrosine kinase , tyrosine phosphorylation , phosphatidylinositol , complement receptor , protein kinase c , integrin alpha m , kinase , signal transduction , biochemistry , receptor , complement system , immunology , antibody
Macrophage‐stimulating protein (MSP) promotes the phagocytosis of C3bi‐coated erythrocytes by resident peritoneal macrophages, although the mechanism by which this occurs is largely unknown. We show that MSP‐induced complement‐mediated phagocytosis requires the RON receptor tyrosine kinase and the αMβ2 integrin, as evidenced by the inability of RON−/− and αM−/− peritoneal macrophages to augment phagocytosis of complement‐coated sheep erythrocytes in response to MSP. MSP stimulation of macrophages results in tyrosine phosphorylation and AKT activation, and inhibitor studies demonstrate a phagocytic requirement for tyrosine kinase and phosphatidylinositol 3‐kinase (PI‐3K) activity as well as activity of the atypical protein kinase C (PKC) isoform ζ, which localizes to MSP‐induced phagosomes containing complement‐coated beads. Additionally, MSP augments the ability of peritoneal macrophages to bind to intercellular adhesion molecule‐1 (ICAM‐1) via the αMβ2 integrin. MSP‐induced ICAM‐1 adhesion is also dependent on tyrosine kinase activity, PI‐3K, and PKC ζ, indicating that these signaling requirements are upstream of complement receptor 3 activation.