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

被引:207
作者
Fitzer-Attas, CJ
Lowry, M
Crowley, MT
Finn, AJ
Meng, FY
DeFranco, AL
Lowell, CA
机构
[1] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, George Williams Hooper Fdn, San Francisco, CA 94143 USA
关键词
actin polymerization; Fc gamma receptors; macrophage; phagocytosis; Src family kinases;
D O I
10.1084/jem.191.4.669
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macrophage Fc gamma receptors (Fc gamma Rs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined Fc gamma R signaling and phagocytic function in bone marrow-derived macrophages from mutant mice lacking the major Src family kinases ex pressed in these cells, Hck, Fgr, and Lyn. Many Fc gamma 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 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 Fc gamma R-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since Fc gamma R-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src fan-Lily kinases are not absolutely required for uptake of IgG-opsonized particles.
引用
收藏
页码:669 / 681
页数:13
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