Role of PSGL-1 binding to selectins in leukocyte recruitment
Role of PSGL-1 binding to selectins in leukocyte recruitment
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DOI：
10.1172/jci119556
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发表时间：
1997-08-01
影响因子：
15.9
通讯作者：
Cummings, RD
中科院分区：
文献类型：
--
作者：
McEver, RP;Cummings, RD
一系列多步骤的粘附和信号事件调节对感染或损伤的炎症反应（1-3）。为了启动这些反应，循环中的白细胞必须在剪切力的作用下粘附在血管壁上。选择素介导第一个粘附步骤，其特征是白细胞在内皮细胞、血小板或其他白细胞上捆绑和滚动（4,5）。l -选择素在大多数白细胞上表达，与一些内皮细胞和其他白细胞上的配体结合。e-选择素在细胞因子激活的内皮细胞上表达，与大多数白细胞的配体结合。p -选择素在活化的血小板和内皮细胞上表达，也与大多数白细胞上的配体结合。选择素及其配体的调控表达有助于启动和终止炎症反应。然而，这些分子的不适当表达有助于白细胞介导的各种炎症和血栓性疾病的组织损伤(6)。每种选择素都是1型膜糖蛋白，具有nh2末端c型凝集素结构域，随后是egf样结构域，一系列短一致重复，跨膜结构域和短细胞质尾。选择素通过凝集素结构域与特定糖缀合配体的相互作用介导细胞-细胞粘附。像其他哺乳动物凝集素一样，选择素选择性地结合特定的低聚糖，但亲和力较低。所有选择都与四糖sialyl Lewis x （sLex; 1 NeuAc 2,3gal 1,4 [Fuc 1,3] GlcNAc）及其异构体sialyl Lewis a （sLea; NeuAc 2,3gal 1,3 [Fuc 1,4] GlcNAc）结合。l -和p -选择素，但不是e -选择素，也结合特定的硫酸化碳水化合物，如硫酸肝素，缺乏唾液酸和焦点（4,5,7）。然而，选择素仅与少数糖蛋白具有较高的亲和力或亲和性。其中大多数是粘蛋白，即具有多个丝氨酸/丝氨酸连接的低聚糖（o -聚糖）和重复肽基序的糖蛋白（4,5）。一个关键的问题是这些分子是否介导了与选择素的生物学相关的相互作用(7)。这一观点侧重于p -选择蛋白糖蛋白配体-1 (PSGL-1)，这是一种涎粘液蛋白，具有最明确的选择蛋白配体功能。
A multistep series of adhesive and signaling events regulates inflammatory responses to infection or injury (1–3). To initiate these responses, circulating leukocytes must adhere to the vascular wall under shear forces. Selectins mediate the first adhesive step, which is characterized by tethering and rolling of leukocytes on endothelial cells, platelets, or other leukocytes (4, 5). L-selectin, expressed on most leukocytes, binds to ligands on some endothelial cells and on other leukocytes. E-selectin, expressed on cytokine-activated endothelial cells, binds to ligands on most leukocytes. P-selectin, expressed on activated platelets and endothelial cells, also binds to ligands on most leukocytes. The regulated expression of the selectins and their ligands helps initiate and terminate the inflammatory response. However, inappropriate expression of these molecules contributes to leukocyte-mediated tissue damage in a variety of inflammatory and thrombotic disorders (6). Each selectin is a type 1 membrane glycoprotein with an NH2-terminal C-type lectin domain, followed by an EGF-like domain, a series of short consensus repeats, a transmembrane domain, and a short cytoplasmic tail. Selectins mediate cell–cell adhesion through interactions of the lectin domains with specific glycoconjugate ligands. Like other mammalian lectins, the selectins bind selectively, but with low affinity, to particular oligosaccharides. All selectins bind to the tetrasaccharide sialyl Lewis x (sLex; 1 NeuAc 2, 3Gal 1, 4 [Fuc 1, 3] GlcNAc) and its isomer sialyl Lewis a (sLea; NeuAc 2, 3Gal 1, 3 [Fuc 1, 4] GlcNAc). L-and P-selectins, but not E-selectin, also bind to particular sulfated carbohydrates, such as heparan sulfate, that lack sialic acid and fucose (4, 5, 7). However, selectins bind with higher affinity or avidity to only a few glycoproteins. Most of these are mucins, ie, glycoproteins with multiple Ser/Thr-linked oligosaccharides (O-glycans) and repeating peptide motifs (4, 5). A key issue is whether any of these molecules mediates biologically relevant interactions with selectins (7). This perspective focuses on P-selectin glycoprotein ligand-1 (PSGL-1), a sialomucin with the most clearly defined function as a selectin ligand.