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Original Article |
Receptormediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn
Correspondence to: Clifford A. Lowell, Department of Laboratory Medicine, University of California at San Francisco, 513 Parnassus Ave., San Francisco, CA 94143. Tel:415-476-2963 Fax:415-502-6497 E-mail:clowell{at}cgl.ucsf.edu.
Macrophage Fc
receptors (Fc
Rs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined Fc
R signaling and phagocytic function in bone marrowderived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many Fc
R-induced functional responses and signaling events were diminished or delayed in these macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signalregulated kinases 1 and 2. Significant reduction of IgG-dependent phagocytosis was not seen in hck-/-fgr-/- or lyn-/- cells, although the single mutant lyn-/- macrophages did manifest signaling defects. Thus, Src family kinases clearly have roles in two events leading to Fc
R-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since Fc
R-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src family kinases are not absolutely required for uptake of IgG-opsonized particles.
Key Words:
actin polymerization, Fc
receptors, macrophage, phagocytosis, Src family kinases
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