An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed on endothelial cells and promotes neutrophil rolling in inflammation
An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed on endothelial cells and promotes neutrophil rolling in inflammation
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DOI：
10.1182/blood-2008-04-153866
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发表时间：
2008-12-15
期刊：
影响因子：
20.3
通讯作者：
Hirata, Takako
中科院分区：
文献类型：
--
作者：
Shigeta, Akiko;Matsumoto, Masanori;Hirata, Takako
从血液中募集的中性粒细胞是先天免疫反应的关键参与者。选择素通过介导中性粒细胞在炎症小静脉中的束缚和滚动在中性粒细胞募集中起关键作用。虽然P-和E-选择素在这一过程中的作用是很好地建立，L-选择素介导的中性粒细胞募集的机制仍然难以捉摸。一种建议是，系留是由流动的中性粒细胞上的L-选择素与粘附的中性粒细胞上的P-选择素糖蛋白配体-I（PSGL-1）相互作用介导的。为了阐明L-选择素介导的中性粒细胞募集是否完全依赖于PSGL-1，我们研究了L-选择素缺乏对PSGL-1缺乏背景小鼠的影响。L-选择素和PSGL-1双敲除小鼠表现出较高的增加，在他们的外周血中性粒细胞计数和更严重的缺陷，在中性粒细胞招募到发炎的腹膜比PSGL-1缺陷的小鼠。炎症提睾肌小静脉的活体显微镜检查显示，L-选择素缺乏或L-选择素的抗体阻断减少了PSGL-1缺陷小鼠中残留的白细胞滚动。流式细胞仪分析表明，从提睾肌内皮细胞结合L-选择素在PSGL-1的独立的方式。这些结果为炎症中存在不同于PSGL-1的L-选择素配体提供了证据，并表明这种配体在内皮细胞上表达，促进体内中性粒细胞滚动。（血。2008;112：4915-4923）
Neutrophils recruited from the blood are key players in the innate immune response. Selectins play critical roles in neutrophil recruitment by mediating their tethering and rolling in inflamed venules. While the roles of P- and E-selectin in this process are well established, the mechanisms of L-selectin-mediated neutrophil recruitment remain elusive. One proposal is that tethering is mediated by L-selectin on flowing neutrophils interacting with P- selectin glycoprotein ligand-1 (PSGL-1) on adherent neutrophils. To clarify whether L-selectin-mediated neutrophil recruitment depends entirely on PSGL-1, we examined the impact of L-selectin deficiency in mice with a PSGL-1 deficient background. L-selectin and PSGL-1 double-knockout mice exhibited a higher increase in their peripheral blood neutrophil count and a worse defect in neutrophil recruitment into the inflamed peritoneum than PSGL-1-deficient mice. Intravital microscopy of inflamed cremaster muscle venules showed that L-selectin deficiency or antibody blockade of L-selectin reduced the residual leukocyte rolling in PSGL-1-deficient mice. Flow cytometric analyses showed that the endothelial cells from the cremaster muscle bound L-selectin in a PSGL-1-independent manner. These results provide evidence for the existence of an L-selectin ligand distinct from PSGL-1 in inflammation and indicate that such a ligand is expressed on endothelial cells, promoting neutrophil rolling in vivo. (Blood. 2008;112:4915-4923)