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趋化因子诱导人中性粒细胞聚集过程中的脱颗粒、膜添加及形态变化

Degranulation, membrane addition, and shape change during chemotactic factor-induced aggregation of human neutrophils.

作者信息

Hoffstein S T, Friedman R S, Weissmann G

出版信息

J Cell Biol. 1982 Oct;95(1):234-41. doi: 10.1083/jcb.95.1.234.

DOI:10.1083/jcb.95.1.234
PMID:7142287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2112338/
Abstract

Neutrophils stimulated by the chemotactic factor formyl-methionyl-leucyl-phenyl-alanine (FMLP) undergo a transient change in surface properties that permits the cells to adhere more readily to surfaces and to each other. This transient change can be monitored by light scattering as stimulated neutrophils form aggregates while stirred in a platelet aggregometer. Maximum change in light scattering occurs within 1 min and correlates with an increase in the percentage of cells that are in aggregates of four or more cells and a decrease in the percentage of single cells. With time (3-5 min), small aggregates disappear and single cells reappear. The transient change in adhesiveness is accompanied by a persistent change in cell shape; the cells become polarized and protrude ruffles from one sector of the cell surface. During aggregation the cells adhere to one another with smooth sides together and ruffles pointed outward. During disaggregation the cells dissociate laterally with the simultaneous internalization of membrane in the region opposite the ruffles. Particle bound to the surface by charge (thorotrast, cationized ferritin) are concentrated and internalized in this region. The change in cell shape from round to ruffled occurs within seconds, suggesting that membrane is added to the cell surface from an intracellular store. We therefore quantified surface membrane by electron microscopy morphometry and measured a 25% increase within 10 s of adding FMLP. The source of new membrane appeared to be the specific granule membrane since the kinetics of granule discharge (between 30% and 50% of all release occurs in the first 10 s) correlate with the appearance of new membrane. Furthermore, the amount of membrane that appears at the cell surface at 10 s correlates with that lost from intracellular granules in that time. Chemotaxin-induced aggregation thus begins with granule discharge and membrane addition followed by protrusion of ruffles. Adherence is maximal at 60 s and the gradual loss of adhesiveness that follows is associated with uropod formation and enhanced endocytic activity.

摘要

受趋化因子甲酰甲硫氨酰亮氨酰苯丙氨酸(FMLP)刺激的中性粒细胞会经历表面特性的短暂变化,这种变化使细胞更容易附着于表面以及彼此之间相互附着。当受刺激的中性粒细胞在血小板聚集仪中搅拌时形成聚集体,这种短暂变化可以通过光散射进行监测。光散射的最大变化在1分钟内出现,并且与四个或更多细胞聚集体中细胞百分比的增加以及单个细胞百分比的减少相关。随着时间推移(3 - 5分钟),小聚集体消失,单个细胞重新出现。粘附性的短暂变化伴随着细胞形状的持续改变;细胞变得极化,并从细胞表面的一个区域伸出褶皱。在聚集过程中,细胞彼此以光滑面相对、褶皱向外的方式相互粘附。在解聚过程中,细胞从侧面解离,同时在与褶皱相对的区域发生膜的内化。通过电荷结合在表面的颗粒(钍造影剂、阳离子化铁蛋白)在该区域被浓缩并内化。细胞形状从圆形变为有褶皱形在数秒内发生,这表明膜是从细胞内储存库添加到细胞表面的。因此,我们通过电子显微镜形态测量法定量了表面膜,并测量到在添加FMLP后10秒内表面膜增加了25%。新膜的来源似乎是特异性颗粒膜,因为颗粒释放的动力学(所有释放的30%至50%发生在最初10秒内)与新膜的出现相关。此外,在10秒时出现在细胞表面的膜量与在该时间内从细胞内颗粒丢失的膜量相关。因此,趋化因子诱导的聚集始于颗粒释放和膜添加,随后是褶皱的突出。粘附性在60秒时达到最大值,随后粘附性的逐渐丧失与尾足形成和增强的内吞活性有关。

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