Yan H C, Williams J P, Christofidou-Solomidou M, Delisser H M, Albelda S M
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Cell Adhes Commun. 1996 Apr;3(6):475-86. doi: 10.3109/15419069609081024.
The purpose of this study was to examine the role of selectins and CD18 cell adhesion molecules (CAMs) in inflammation induced by injection of leukotriene B4 (LTB4) into human skin. To accomplish this, the expression of CAMs and the ability of specific antibodies against CAMs to block white blood cell (WBC) transmigration were studied in an in vivo model consisting of human skin transplanted onto mice with the severe combined immune deficiency (SCID) mutation. The results indicate that LTB4-induced WBC transmigration in the human/SCID model is rapid and pronounced; however, it is not accompanied by a significant upregulation of the baseline expression of endothelial P-selectin, E-selectin, ICAM-1 or VCAM-1. An anti-murine CD18 mAb markedly inhibited white cell infiltration (89% inhibition) confirming the importance of beta 2 integrins in the process. The role of selectins was also examined. MEL-14, a bioactive antibody against murine L-selectin inhibited transmigration by 66%. A significant, but smaller, effect (39% inhibition) was observed by blocking E-selectin function. These results indicate that LTB4-induced inflammation does not require upregulation of endothelial CAM expression and, in contrast to TNF alpha-induced transmigration, is only partially blocked by anti-E-selectin antibodies.
本研究的目的是探讨选择素和CD18细胞黏附分子（CAMs）在将白三烯B4（LTB4）注射入人体皮肤所诱导的炎症中的作用。为实现这一目的，在一个由移植到具有严重联合免疫缺陷（SCID）突变小鼠身上的人体皮肤组成的体内模型中，研究了CAMs的表达以及针对CAMs的特异性抗体阻断白细胞（WBC）迁移的能力。结果表明，在人/SCID模型中，LTB4诱导的WBC迁移迅速且明显；然而，它并未伴随着内皮P选择素、E选择素、ICAM-1或VCAM-1基线表达的显著上调。一种抗小鼠CD18单克隆抗体显著抑制了白细胞浸润（89%的抑制率），证实了β2整合素在此过程中的重要性。还研究了选择素的作用。MEL-14，一种针对小鼠L选择素的生物活性抗体，抑制迁移达66%。通过阻断E选择素功能观察到显著但较小的效应（39%的抑制率）。这些结果表明，LTB4诱导的炎症不需要上调内皮CAM的表达，并且与TNFα诱导的迁移相反，仅被抗E选择素抗体部分阻断。
