Department of Biomedical Engineering, Graduate Group in Immunology, University of California, Davis CA, USA.
Front Immunol. 2012 Jul 10;3:188. doi: 10.3389/fimmu.2012.00188. eCollection 2012.
Leukocyte trafficking to acute sites of injury or infection requires spatial and temporal cues that fine tune precise sites of firm adhesion and guide migration to endothelial junctions where they undergo diapedesis to sites of insult. Many detailed studies on the location and gradient of chemokines such as IL-8 and other CXCR ligands reveal that their recognition shortly after selectin-mediated capture and rolling exerts acute effects on integrin activation and subsequent binding to their ligands on the endothelium, which directs firm adhesion, adhesion strengthening, and downstream migration. In this process, G-protein coupled receptor (GPCR) signaling has been found to play an integral role in activating and mobilizing intracellular stores of calcium, GTPases such as Rap-1 and Rho and cytokeletal proteins such as Talin and F-actin to facilitate cell polarity and directional pseudopod formation. A critical question remaining is how intracellular Ca(2+) flux from CRAC channels such as Orai1 synergizes with cytosolic stores to mediate a rapid flux which is critical to the onset of PMN arrest and polarization. Our review will highlight a specific role for calcium as a signaling messenger in activating focal clusters of integrins bound to the cytoskeleton which allows the cell to attain a migratory phenotype. The precise interplay between chemokines, selectins, and integrins binding under the ubiquitous presence of shear stress from blood flow provides an essential cooperative signaling mechanism for effective leukocyte recruitment.
白细胞向急性损伤或感染部位的迁移需要时空线索，以精细调节牢固黏附的精确部位，并引导迁移到内皮连接处，在该处它们通过血管穿透到达损伤部位。许多关于趋化因子（如 IL-8 和其他 CXCR 配体）的位置和梯度的详细研究表明，它们在选择素介导的捕获和滚动后不久被识别，会对整合素的激活产生急性影响，并随后与内皮上的配体结合，从而指导牢固黏附、黏附强化和下游迁移。在这个过程中，已发现 G 蛋白偶联受体 (GPCR) 信号在激活和动员细胞内钙储存、Rap-1 和 Rho 等 GTPases 以及 Talin 和 F-肌动蛋白等细胞骨架蛋白方面发挥着重要作用，以促进细胞极性和定向伪足形成。仍然存在的一个关键问题是，CRAC 通道（如 Orai1）中的细胞内 Ca(2+) 通量如何与细胞质储存协同作用，以介导对中性粒细胞捕获和极化起始至关重要的快速通量。我们的综述将强调钙作为信号信使在激活与细胞骨架结合的整联蛋白的焦点簇中的特定作用，这使细胞能够获得迁移表型。趋化因子、选择素和整合素在血流产生的普遍剪切应力下的结合之间的精确相互作用为有效的白细胞募集提供了一种必要的协同信号机制。
