Walter U M, Issekutz A C
Department Pediatrics and Microbiology-Immunology, Dalhousie University, Halifax, Canada.
Eur J Immunol. 1997 Jun;27(6):1498-505. doi: 10.1002/eji.1830270628.
The role of the endothelial adhesion molecules E- and P-selectin in leukocyte accumulation in arthritis is not known. We investigated this role in rat adjuvant arthritis by employing adhesion function-blocking monoclonal antibodies (mAb) to rat P- and E-selectin. The acute migration (2 h) of radiolabeled rat blood neutrophils and monocytes to joints and skin was determined. Anti-P-selectin mAb significantly reduced accumulation of monocytes (by 50%) and neutrophils (by 40%) in the talar joint, and of neutrophils in tail joints (by 90%). Anti-E-selectin mAb alone did not attenuate leukocyte migration, but when combined with anti-P-selectin mAb, it enhanced inhibition of neutrophil accumulation in the talar and carpal joints. In the same animals, anti-P-selectin mAb significantly inhibited neutrophil and monocyte migration to dermal inflammatory reactions induced by zymosan-activated rat serum (ZAS) containing the chemotactic factor C5ades Arg, endotoxin (LPS), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In contrast, anti-E-selectin mAb alone had no effect on monocyte or neutrophil accumulation in inflamed skin of arthritic animals, but again enhanced the inhibition when combined with mAb to P-selectin. The addition of anti-L-selectin mAb to anti-P- and E-selectin mAb did not further suppress monocyte or neutrophil migration to inflamed skin or joints. These results demonstrate that optimal leukocyte migration to arthritic joints and inflamed skin is P-selectin dependent, and E-selectin is not essential. However, E-selectin contributes to migration when P-selectin mechanisms are not operative. L-selectin does not play a role in E- and P-selectin-independent leukocyte migration to joints or skin inflammation in arthritic rats. However, it is likely that additional selectin-independent pathways also mediate neutrophil and monocyte migration to joint and skin inflammation.
内皮黏附分子E-选择素和P-选择素在关节炎中白细胞积聚过程中的作用尚不清楚。我们通过使用针对大鼠P-选择素和E-选择素的黏附功能阻断单克隆抗体（mAb），在大鼠佐剂性关节炎中研究了这一作用。测定了放射性标记的大鼠血液中性粒细胞和单核细胞向关节和皮肤的急性迁移（2小时）。抗P-选择素mAb显著减少了距骨关节中单核细胞（减少50%）和中性粒细胞（减少40%）以及尾关节中中性粒细胞（减少90%）的积聚。单独使用抗E-选择素mAb并未减弱白细胞迁移，但与抗P-选择素mAb联合使用时，它增强了对距骨和腕关节中中性粒细胞积聚的抑制作用。在同一动物中，抗P-选择素mAb显著抑制了中性粒细胞和单核细胞向由含有趋化因子C5ades Arg、内毒素（LPS）、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）的酵母聚糖激活的大鼠血清（ZAS）诱导的皮肤炎症反应的迁移。相比之下，单独使用抗E-选择素mAb对关节炎动物炎症皮肤中的单核细胞或中性粒细胞积聚没有影响，但与抗P-选择素mAb联合使用时再次增强了抑制作用。将抗L-选择素mAb添加到抗P-和E-选择素mAb中并没有进一步抑制单核细胞或中性粒细胞向炎症皮肤或关节的迁移。这些结果表明，白细胞向关节炎关节和炎症皮肤的最佳迁移依赖于P-选择素，而E-选择素并非必需。然而，当P-选择素机制不起作用时，E-选择素有助于迁移。L-选择素在关节炎大鼠中与E-选择素和P-选择素无关的白细胞向关节或皮肤炎症的迁移中不起作用。然而，很可能还有其他不依赖选择素的途径也介导中性粒细胞和单核细胞向关节和皮肤炎症的迁移。
