Edberg J C, Moon J J, Chang D J, Kimberly R P
Division of Clinical Immunology and Rheumatology, Departments of Medicine and Microbiology, University of Alabama, Birmingham, Alabama 35294, USA.
J Biol Chem. 1998 Apr 3;273(14):8071-9. doi: 10.1074/jbc.273.14.8071.
Human neutrophils express two structurally distinct receptors for the Fc region of IgG, FcgammaRIIa and FcgammaRIIIb. Although earlier studies have suggested that the functional properties of these receptors are similar, mounting evidence suggests that these receptors are capable of inducing distinct functional responses. Accordingly, we have examined the regulation of intracellular Ca2+ transients induced by each of these receptors alone (homotypic receptor cross-linking) and together (heterotypic receptor cross-linking). The glycosylphosphatidylinositol-anchored FcgammaRIIIb induces a rise in [Ca2+] after homotypic cross-linking that is independent of ligand-mediated engagement of the transmembrane FcgammaRIIa. Both receptors were sensitive to the protein-tyrosine kinase inhibitor methyl 2,5-dihydroxycinnamate, but FcgammaRIIa-induced signaling was uniquely sensitive to the protein-tyrosine kinase inhibitor genistein. FcgammaRIIa but not FcgammaRIIIb engages a cAMP-sensitive and inositol 1,4, 5-trisphosphate-dependent pathway(s) that results in the Ca2+-transient. When these receptors are cross-linked into heterotypic clusters, a synergistic rise in [Ca2+] is observed that is accompanied by synergistic increases in the phospholipase Cgamma-breakdown products inositol 1,4,5-trisphosphate and diglyceride. These data provide a mechanism for the functional differences between these two receptors and suggest the possibility that they can be differentially modulated.
人类中性粒细胞表达两种结构不同的IgG Fc区受体，即FcγRIIa和FcγRIIIb。尽管早期研究表明这些受体的功能特性相似，但越来越多的证据表明这些受体能够诱导不同的功能反应。因此，我们研究了单独由这些受体中的每一种诱导的细胞内Ca2+瞬变的调节（同型受体交联）以及一起诱导的调节（异型受体交联）。糖基磷脂酰肌醇锚定的FcγRIIIb在同型交联后诱导[Ca2+]升高，这独立于跨膜FcγRIIa的配体介导的结合。两种受体都对蛋白酪氨酸激酶抑制剂2,5-二羟基肉桂酸甲酯敏感，但FcγRIIa诱导的信号传导对蛋白酪氨酸激酶抑制剂染料木黄酮具有独特的敏感性。FcγRIIa而非FcγRIIIb参与了一条对cAMP敏感且依赖肌醇1,4,5-三磷酸的途径，该途径导致Ca2+瞬变。当这些受体交联形成异型簇时，观察到[Ca2+]协同升高，同时磷脂酶Cγ分解产物肌醇1,4,5-三磷酸和甘油二酯也协同增加。这些数据为这两种受体之间的功能差异提供了一种机制，并表明它们可能受到不同调节的可能性。
