Simon S I, Cherapanov V, Nadra I, Waddell T K, Seo S M, Wang Q, Doerschuk C M, Downey G P
Department of Pediatrics, Section of Leukocyte Biology, Baylor College of Medicine, Houston, TX 77030, USA.
J Immunol. 1999 Sep 1;163(5):2891-901.
Ligation and clustering of L-selectin by Ab ("cross-linking") or physiologic ligands results in activation of diverse responses that favor enhanced microvascular sequestration and emigration of neutrophils. The earliest responses include a rise in intracellular calcium, enhanced tyrosine phosphorylation, and activation of extracellular signal-regulated kinases. Additionally, cross-linking of L-selectin induces sustained shape change and activation of beta2 integrins, leading to neutrophil arrest under conditions of shear flow. In this report, we examined several possible mechanisms whereby transmembrane signals from L-selectin might contribute to an increase in the microvascular retention of neutrophils and enhanced efficiency of emigration. In human peripheral blood neutrophils, cross-linking of L-selectin induced alterations in cellular biophysical properties, including a decrease in cell deformability associated with F-actin assembly and redistribution, as well as enhanced adhesion of microspheres bound to beta2 integrins. L-selectin and the beta2 integrin became spatially colocalized as determined by confocal immunofluorescence microscopy and fluorescence resonance energy transfer. We conclude that intracellular signals from L-selectin may enhance the microvascular sequestration of neutrophils at sites of inflammation through a combination of cytoskeletal alterations leading to cell stiffening and an increase in adhesiveness mediated through alterations in beta2 integrins.
通过抗体（“交联”）或生理配体对L-选择素进行结扎和聚集，会引发多种反应，这些反应有利于增强微血管中嗜中性粒细胞的滞留和迁移。最早的反应包括细胞内钙升高、酪氨酸磷酸化增强以及细胞外信号调节激酶的激活。此外，L-选择素的交联会诱导持续的形态变化和β2整合素的激活，导致嗜中性粒细胞在剪切流条件下停滞。在本报告中，我们研究了几种可能的机制，通过这些机制，来自L-选择素的跨膜信号可能有助于增加嗜中性粒细胞在微血管中的滞留以及提高迁移效率。在人外周血嗜中性粒细胞中，L-选择素的交联诱导了细胞生物物理特性的改变，包括与F-肌动蛋白组装和重新分布相关的细胞变形性降低，以及与β2整合素结合的微球的粘附增强。通过共聚焦免疫荧光显微镜和荧光共振能量转移确定，L-选择素和β2整合素在空间上共定位。我们得出结论，来自L-选择素的细胞内信号可能通过导致细胞变硬的细胞骨架改变以及通过β2整合素改变介导的粘附性增加的组合，增强炎症部位嗜中性粒细胞在微血管中的滞留。
