An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane.
An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane.
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DOI：
10.1084/jem.184.1.229
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发表时间：
1996-07-01
期刊：
影响因子：
--
通讯作者：
Nourshargh S
中科院分区：
文献类型：
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作者：
Wakelin MW;Sanz MJ;Dewar A;Albelda SM;Larkin SW;Boughton-Smith N;Williams TJ;Nourshargh S
血小板-内皮细胞粘附分子-1（PECAM-1，CD 31）在体外白细胞通过培养的内皮细胞迁移的过程中起着积极的作用，抗PECAM-1抗体（Abs）在体内抑制白细胞聚集到炎症部位。尽管有后者，但仍不清楚PECAM-1在体内白细胞迁移的哪个阶段参与。为了直接解决这一点，我们研究了抗PECAM-1抗体，识别大鼠PECAM-1，白细胞反应在大鼠肠系膜微血管使用活体显微镜。在由白细胞介素（IL）-1 β激活的肠系膜制备物中，抗PECAM-1 Ab对白细胞的滚动或粘附无显著影响，但以剂量依赖性方式抑制其迁移至周围血管外组织。尽管在某些血管节段中，这些白细胞在血管腔内停止，但通常白细胞似乎被困在血管壁内。通过电子显微镜对这些切片进行分析，发现白细胞已穿过内皮细胞连接部，但未穿过基底膜。与Ab在用IL-1 β处理的肠系膜制备物中的作用相反，抗PECAM-1 Ab不抑制局部或腹膜内施用趋化肽甲酰基-甲硫氨酰基-亮氨酰基-苯丙氨酸诱导的白细胞外渗。这些结果直接证明了PECAM-1在体内白细胞外渗中的作用，并表明这种参与对于某些炎症介质引起的白细胞外渗是选择性的。此外，我们的研究结果提供了第一个在体内的迹象表明，PECAM-1可能有一个重要的作用，触发通过血管周围基底膜的白细胞。
Platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) plays an active role in the process of leukocyte migration through cultured endothelial cells in vitro and anti-PECAM-1 antibodies (Abs) inhibit accumulation of leukocytes into sites of inflammation in vivo. Despite the latter, it is still not clear at which stage of leukocyte emigration in vivo PECAM-1 is involved. To address this point directly, we studied the effect of an anti-PECAM-1 Ab, recognizing rat PECAM-1, on leukocyte responses within rat mesenteric microvessels using intravital microscopy. In mesenteric preparations activated by interleukin (IL)-1 beta, the anti-PECAM-1 Ab had no significant effect on the rolling or adhesion of leukocytes, but inhibited their migration into the surrounding extravascular tissue in a dose-dependent manner. Although in some vessel segments these leukocytes had come to a halt within the vascular lumen, often the leukocytes appeared to be trapped within the vessel wall. Analysis of these sections by electron microscopy revealed that the leukocytes had passed through endothelial cell junctions but not the basement membrane. In contrast to the effect of the Ab in mesenteric preparations treated with IL-1 beta, leukocyte extravasation induced by topical or intraperitoneal administration of the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was not inhibited by the anti-PECAM-1 Ab. These results directly demonstrate a role for PECAM-1 in leukocyte extravasation in vivo and indicate that this involvement is selective for leukocyte extravasation elicited by certain inflammatory mediators. Further, our findings provide the first in vivo indication that PECAM-1 may have an important role in triggering the passage of leukocytes through the perivascular basement membrane.