Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition
Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition
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DOI：
10.1016/s0002-9440(10)64279-4
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发表时间：
2003-05-01
影响因子：
6
通讯作者：
Sato, S
中科院分区：
文献类型：
--
作者：
Yanaba, K;Kaburagi, Y;Sato, S
免疫复合物诱导的组织损伤由炎性细胞浸润介导，炎性细胞浸润受多种粘附分子高度调节。为了评估粘附分子（包括选择素和ICAM-1）在该发病过程中的相对贡献，在缺乏E-选择素、P-选择素或L-选择素和ICAM-1的小鼠中用抗P-或E-选择素mAb检查皮肤被动Arthus反应。与野生型小鼠相比，P-选择素（-/-）小鼠的水肿和出血显著减少，而E-选择素（-/-）小鼠的水肿和出血没有受到抑制。相对于L-选择素/ICAM-1（-/-）以及P-选择素（-/-）小鼠，组合的E-和P-选择素阻断导致更显著的降低。值得注意的是，在L-选择素/ICAM-1（-/-）小鼠中E-和P-选择素阻断完全消除了水肿和出血。抑制水肿和出血可减少中性粒细胞和肥大细胞的浸润，这些细胞表达显著水平的P-选择素糖蛋白配体-1。同样，在腹膜Arthus反应中观察到中性粒细胞和肥大细胞浸润减少，部分与肿瘤坏死因子-α和白细胞介素-6的产生减少相关。这项研究的结果表明，这两种内皮选择素主要是通过调节肥大细胞和中性粒细胞浸润的Arthus反应，并充分发展的Arthus反应介导的所有选择素和ICAM-1的合作。
Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the relative contribution of adhesion molecules, including selectins and ICAM-1, in this pathogenetic process, the cutaneous passive Arthus reaction was examined in mice lacking E-selectin, P-selectin, or both L-selectin and ICAM-1 with anti-P- or E-selectin mAbs. Edema and hemorrhage were significantly reduced in P-selectin(-/-) mice compared with wild-type mice while they were not inhibited in E-selectin(-/-) mice. Combined E- and P-selectin blockade resulted in more significant reduction relative to L-selectin/ICAM-1(-/-) as well as P-selectin(-/-) mice. Remarkably, both E-and P-selectin blockade in L-selectin/ICAM-1(-/-) mice completely abrogated edema and hemorrhage. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells that expressed significant levels of P-selectin glycoprotein ligand-1. Similarly reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated partly with the decreased production of tumor necrosis factor-alpha and interleukin-6. The results of this study indicate that both endothelial selectins contribute predominantly to the Arthus reaction by regulating mast cell and neutrophil infiltration and that the full development of the Arthus reaction is mediated cooperatively by all selectins and ICAM-1.