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Published online before print May 22, 2003

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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0602319

Received for publication June 21, 2002.
Revised January 20, 2003.
Accepted for publication January 29, 2003.

Article

Activation of CR3-mediated phagocytosis binding by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3-kinase, and protein kinase C

Department of Veterinary Science, Pennsylvania State University, Pathobiology Graduate Program, University Park

^@ To whom correspondence should be addressed. E-mail: phc7{at}psu.edu.

	Abstract

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 reorienting negativity (RON) receptor tyrosine kinase and the M2 integrin, as evidenced by the inability of RON-/- and M-/- 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 , 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 M2 integrin. MSP-induced ICAM-1 adhesion is also dependent on tyrosine kinase activity, PI-3K, and PKC , indicating that these signaling requirements are upstream of complement receptor 3 activation.

Key Words: macrophage-stimulating protein • complement receptor 3 • intracellular adhesion molecule-1

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