Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration.
Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration.
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DOI：
10.1084/jem.190.12.1769
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发表时间：
1999-12-20
期刊：
影响因子：
--
通讯作者：
Furie B
中科院分区：
文献类型：
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作者：
Yang J;Hirata T;Croce K;Merrill-Skoloff G;Tchernychev B;Williams E;Flaumenhaft R;Furie BC;Furie B
P-selectin glycoprotein ligand 1（PSGL-1）是一种粘蛋白样选择素反受体，可与P-选择素、E-选择素和L-选择素结合。为了确定其在细胞粘附中作为炎症期间白细胞滚动和迁移的介体的生理作用，我们通过靶向破坏PSGL-1基因来制备PSGL-1遗传缺陷的小鼠。纯合子PSGL-1缺陷型小鼠存活且可生育。血液中性粒细胞计数中度升高。无自发性皮肤溃疡或感染的证据。化学性腹膜炎模型中的白细胞浸润显著延迟。白细胞滚动在体内，研究了活体显微镜在毛细血管后小静脉的提睾肌，显着减少创伤后30分钟在PSGL-1缺陷的小鼠。相比之下，肿瘤坏死因子α刺激后2小时的白细胞滚动仅略有减少，但注入PSGL-1缺陷小鼠的E-选择素阻断抗体几乎完全消除了白细胞滚动。这些结果表明，PSGL-1是所需的早期炎症反应，但不是E-选择素介导的反应。这些动力学与PSGL-1是主要的嗜中性粒细胞P-选择素配体但不是体内生理条件下E-选择素所需的反受体的模型一致。
P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like selectin counterreceptor that binds to P-selectin, E-selectin, and L-selectin. To determine its physiological role in cell adhesion as a mediator of leukocyte rolling and migration during inflammation, we prepared mice genetically deficient in PSGL-1 by targeted disruption of the PSGL-1 gene. The homozygous PSGL-1–deficient mouse was viable and fertile. The blood neutrophil count was modestly elevated. There was no evidence of spontaneous development of skin ulcerations or infections. Leukocyte infiltration in the chemical peritonitis model was significantly delayed. Leukocyte rolling in vivo, studied by intravital microscopy in postcapillary venules of the cremaster muscle, was markedly decreased 30 min after trauma in the PSGL-1–deficient mouse. In contrast, leukocyte rolling 2 h after tumor necrosis factor α stimulation was only modestly reduced, but blocking antibodies to E-selectin infused into the PSGL-1–deficient mouse almost completely eliminated leukocyte rolling. These results indicate that PSGL-1 is required for the early inflammatory responses but not for E-selectin–mediated responses. These kinetics are consistent with a model in which PSGL-1 is the predominant neutrophil P-selectin ligand but is not a required counterreceptor for E-selectin under in vivo physiological conditions.