Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Munich, Germany.
Cells. 2022 Apr 12;11(8):1310. doi: 10.3390/cells11081310.
As a consequence of tissue injury or infection, neutrophils are recruited in a stepwise recruitment process from the bloodstream into the surrounding tissue. Selectins are a family of adhesion molecules comprised of L-, E-, and P-selectin. Differences in expression patterns, protein structure, and ligand binding characteristics mediate distinct functions of each selectin. Interactions of selectins and their counter-receptors mediate the first contact of neutrophils with the endothelium, as well as subsequent neutrophil rolling along the endothelial surface. For efficient neutrophil recruitment, activation of β-integrins on the cell surface is essential. Integrin activation can be elicited via selectin- as well as chemokine-mediated inside-out signaling resulting in integrin conformational changes and clustering. Dysregulation of selectin-induced integrin activation on neutrophils is involved in the development of severe pathological disease conditions including leukocyte adhesion deficiency (LAD) syndromes in humans. Here, we review molecular mechanisms involved in selectin-mediated signaling pathways in neutrophils and their impact on integrin activation, neutrophil recruitment, and inflammatory diseases.
在组织损伤或感染的情况下，中性粒细胞会通过逐步募集过程从血液中招募到周围组织中。选择素是一类黏附分子，包括 L 选素、E 选素和 P 选素。表达模式、蛋白质结构和配体结合特性的差异调节每种选择素的不同功能。选择素及其对应受体的相互作用介导中性粒细胞与内皮细胞的最初接触，以及随后中性粒细胞沿内皮表面滚动。为了实现有效的中性粒细胞募集，细胞表面β整合素的激活是必不可少的。整合素的激活可以通过选择素和趋化因子介导的内向外信号转导来诱导，导致整合素构象变化和聚集。中性粒细胞中选择素诱导的整合素激活失调与严重病理疾病状况的发展有关，包括人类白细胞黏附缺陷（LAD）综合征。在这里，我们综述了中性粒细胞中参与选择素介导的信号通路的分子机制及其对整合素激活、中性粒细胞募集和炎症性疾病的影响。
