Fcγ receptor–mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn

CJ Fitzer-Attas, M Lowry, MT Crowley, AJ Finn… - The Journal of …, 2000 - rupress.org
CJ Fitzer-Attas, M Lowry, MT Crowley, AJ Finn, F Meng, AL DeFranco, CA Lowell
The Journal of experimental medicine, 2000rupress.org
Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated
viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in
bone marrow–derived macrophages from mutant mice lacking the major Src family kinases
expressed in these cells, Hck, Fgr, and Lyn. Many FcγR-induced functional responses and
signaling events were diminished or delayed in these macrophages, including
immunoglobulin (Ig) G-coated erythrocyte phagocytosis, respiratory burst, actin cup …
Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in bone marrow–derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many FcγR-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 signal–regulated 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 FcγR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcγR-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.
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