Middelhoven P J, van Buul J D, Kleijer M, Roos D, Hordijk P L
Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Biochem Biophys Res Commun. 1999 Feb 24;255(3):568-74. doi: 10.1006/bbrc.1999.0244.
FcgammaRIIIb (CD16) is a glycosyl phosphatidylinositol (GPI)-anchored low-affinity IgG receptor, exclusively expressed on human neutrophils. FcgammaRIIIb associates with complement receptor 3 (CR3, Mac-1, CD11b/CD18), which may indirectly link FcgammaRIIIb to the actin cytoskeleton. Upon neutrophil activation, apoptosis, or chemotaxis, FcgammaRIIIb is shed from the cell surface. In all of these events, actin rearrangements play an important role. To establish a role for the actin cytoskeleton in the control of FcgammaRIIIb shedding, we treated human neutrophils with jasplakinolide, an actin-polymerizing peptide. We show that enhanced actin polymerization induces time- and dose-dependent shedding of FcgammaRIIIb. This effect was not restricted to FcgammaRIIIb, because the cell surface expression of CD43, CD44, and L-selectin was also downregulated after induction of actin polymerization. This actin-dependent pathway is staurosporine sensitive but does not appear to involve activation of PKC or CR3. These data show that the actin cytoskeleton can regulate protein ectodomain shedding from human neutrophils.
FcγRIIIb（CD16）是一种糖基磷脂酰肌醇（GPI）锚定的低亲和力IgG受体，仅在人类中性粒细胞上表达。FcγRIIIb与补体受体3（CR3，Mac-1，CD11b/CD18）相关联，这可能间接将FcγRIIIb与肌动蛋白细胞骨架连接起来。在中性粒细胞激活、凋亡或趋化作用时，FcγRIIIb从细胞表面脱落。在所有这些事件中，肌动蛋白重排都起着重要作用。为了确定肌动蛋白细胞骨架在控制FcγRIIIb脱落中的作用，我们用jasplakinolide（一种肌动蛋白聚合肽）处理人类中性粒细胞。我们发现增强的肌动蛋白聚合诱导FcγRIIIb的时间和剂量依赖性脱落。这种效应并不局限于FcγRIIIb，因为在诱导肌动蛋白聚合后，CD43、CD44和L-选择素的细胞表面表达也下调。这种肌动蛋白依赖性途径对星形孢菌素敏感，但似乎不涉及蛋白激酶C（PKC）或CR3的激活。这些数据表明，肌动蛋白细胞骨架可以调节人类中性粒细胞的蛋白质胞外域脱落。
