Miotla J M, Ridger V C, Hellewell P G
Endothelial Cell Biology Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX.
Br J Pharmacol. 2001 Jun;133(4):550-6. doi: 10.1038/sj.bjp.0704118.
The role of selectins in neutrophil emigration in response to the CXC chemokines KC and MIP-2 was investigated in wild type and P-selectin deficient mice. Intrapleural injection of KC or MIP-2 induced a rapid and specific neutrophil accumulation. Emigration 2 h after KC or MIP-2 was reduced 83 - 88% by anti-L-selectin mAb and 53 - 63% by anti-P-selectin mAb. Co-administration of anti-L- and P-selectin mAbs abolished neutrophil migration induced by either chemokine. An anti-E-selectin mAb tested alone did not affect KC-induced neutrophil migration after 2 or 4 h. Moreover, anti-E-selectin did not have an additive inhibitory effect on KC-induced neutrophil migration compared with P-selectin blockade alone. This was found when neutrophil migration was measured at 2 and 4 h after KC. Despite a blood neutrophilia, neutrophil migration at 2 and 4 h after KC was markedly smaller (by approximately 90%) in P-selectin deficient mice compared with wild type animals. Responses at both time points were not decreased further in animals given E-selectin mAb but were reduced to the PBS control level in the presence of anti-L-selectin. In vitro study of cultured murine endothelial cells demonstrated that KC can directly increase cell surface P-selectin expression. These data suggest that CXC chemokine-induced neutrophil accumulation is dependent on both neutrophil L-selectin and a rapid upregulation of endothelial P-selectin but there is no evidence for E-selectin induction.
在野生型和P-选择素缺陷型小鼠中，研究了选择素在中性粒细胞响应CXC趋化因子KC和MIP-2时的迁移过程中的作用。胸膜腔内注射KC或MIP-2可诱导快速且特异性的中性粒细胞聚集。KC或MIP-2注射2小时后，抗L-选择素单克隆抗体可使中性粒细胞迁移减少83 - 88%，抗P-选择素单克隆抗体可使其减少53 - 63%。同时给予抗L-和P-选择素单克隆抗体可消除由任何一种趋化因子诱导的中性粒细胞迁移。单独测试的抗E-选择素单克隆抗体在2小时或4小时后不影响KC诱导的中性粒细胞迁移。此外，与单独阻断P-选择素相比，抗E-选择素对KC诱导的中性粒细胞迁移没有附加抑制作用。这是在KC注射后2小时和4小时测量中性粒细胞迁移时发现的。尽管存在血液中性粒细胞增多，但与野生型动物相比，P-选择素缺陷型小鼠在KC注射后2小时和4小时的中性粒细胞迁移明显减少（约90%）。给予E-选择素单克隆抗体的动物在两个时间点的反应均未进一步降低，但在存在抗L-选择素的情况下，反应降低至PBS对照水平。对培养的小鼠内皮细胞的体外研究表明，KC可直接增加细胞表面P-选择素的表达。这些数据表明，CXC趋化因子诱导的中性粒细胞聚集既依赖于中性粒细胞L-选择素，也依赖于内皮细胞P-选择素的快速上调，但没有证据表明E-选择素被诱导。
