Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn.
Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn.
复制标题
Fcgamma受体介导的巨噬细胞中缺乏SRC家族酪氨酸激酶HCK，FGR和Lyn的吞噬作用。
DOI：
10.1084/jem.191.4.669
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发表时间：
2000-02-21
影响因子：
15.3
通讯作者：
Lowell, C A
中科院分区：
文献类型：
--
作者：
Fitzer-Attas, C J;Lowry, M;Crowley, M T;Finn, A J;Meng, F;DeFranco, A L;Lowell, C A
巨噬细胞Fcγ受体（FcγRs）介导抗体包被病毒、细菌和寄生虫的摄取和破坏。我们检测了突变小鼠骨髓源性巨噬细胞中FcγR信号传导和吞噬功能，这些细胞缺乏在这些细胞中表达的主要Src家族激酶Hck、Fgr和林恩。在这些巨噬细胞中，许多Fcγ R诱导的功能反应和信号传导事件减少或延迟，包括免疫球蛋白（IG）G包被的红细胞吞噬作用、呼吸爆发、肌动蛋白杯形成以及Syk、磷脂酰肌醇3-激酶和细胞外信号调节激酶1和2的激活。在hck − /−fgr − /−或林恩− /−细胞中未观察到IgG依赖性吞噬作用的显著降低，尽管单个突变的林恩− /−巨噬细胞确实表现出信号传导缺陷。因此，Src家族激酶显然在导致Fcγ R介导的吞噬作用的两个事件中发挥作用，一个涉及肌动蛋白聚合的启动，第二个涉及Syk的激活和随后的内化。由于Fcγ R介导的吞噬作用确实在三重突变体巨噬细胞中以延迟方式以适度水平发生，因此这些Src家族激酶对于IgG调理颗粒的摄取不是绝对必需的。
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.