Platelets Control Leukocyte Recruitment in a Murine Model of Cutaneous Arthus Reaction
Platelets Control Leukocyte Recruitment in a Murine Model of Cutaneous Arthus Reaction
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DOI：
10.2353/ajpath.2010.081117
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发表时间：
2010-01-01
影响因子：
6
通讯作者：
Sato, Shinichi
中科院分区：
文献类型：
--
作者：
Hara, Toshihide;Shimizu, Kazuhiro;Sato, Shinichi
血小板已被证明是重要的炎症，但其作用在皮肤Arthus反应仍不清楚。为了评估血小板在这一发病过程中的作用，在野生型小鼠和缺乏E-选择素、P-选择素或P-选择素糖蛋白配体-1（PSGL-1）的小鼠中检查了皮肤Arthus反应，伴或不伴白消安（一种骨髓前体细胞特异性毒素）的血小板耗竭。与未处理的小鼠相比，白消安处理的野生型小鼠中由免疫复合物激发诱导的水肿和出血显著减少。白消安治疗没有影响水肿和出血的P-选择素或PSGL-1缺陷的小鼠，表明白消安的效果是依赖于P-选择素和PSGL-1的表达。抑制水肿和出血可减少中性粒细胞和肥大细胞的浸润，并降低循环血小板的水平。白细胞介素-6、肿瘤坏死因子-α和血小板衍生趋化因子的皮肤产生增加;在Arthus反应期间，与未治疗的小鼠相比，白消安治疗的野生型小鼠中抑制了白细胞介素-6、肿瘤坏死因子-α和血小板衍生趋化因子的皮肤产生增加，这表明皮肤炎症减少。流式细胞术分析表明，免疫复合物的挑战产生的血液血小板-白细胞聚集体，减少白消安治疗。在血小板减少的小鼠中，免疫复合物激发后的皮肤炎症通过血小板输注而恢复。这些结果表明，血小板通过形成血小板-白细胞聚集体并在炎症部位分泌趋化因子，主要通过血小板上的P-选择素与白细胞上的PSGL-1的相互作用，诱导白细胞募集到皮肤中。(Am J Pathol 2010，176：259-269; DOI：10.2353/ajpath.2010.081117）
Platelets have been shown to be important in inflammation, but their role in the cutaneous Arthus reaction remains unclear. To assess the role of platelets in this pathogenetic process, the cutaneous Arthus reaction was examined in wild-type mice and mice lacking E-selectin, P-selectin, or P-selectin glycoprotein ligand-1 (PSGL-1) with or without platelet depletion by busulfan, a bone marrow precursor cell-specific toxin. Edema and hemorrhage induced by immune complex challenge significantly decreased in busulfan-treated wild-type mice compared with untreated mice. Busulfan treatment did not affect edema and hemorrhage in P-selectin- or PSGL-1-deficient mice, suggesting that the effect by busulfan is dependent on P-selectin and PSGL-1 expression. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells and reduced levels of circulating platelets. increased cutaneous production of interleukin-6, tumor necrosis factor-alpha, and platelet-derived chemokines; during Arthus reaction was inhibited in busulfan-treated wild-type mice relative to untreated mice, which paralleled the reduction in cutaneous inflammation. Flow cytometric analysis showed that immune complex challenge generated blood platelet-leukocyte aggregates that decreased by busulfan treatment. in thrombocytopenic mice, the cutaneous inflammation after immune complex challenge was restored by platelet infusion. These results suggest that platelets induce leukocyte recruitment into skin by forming platelet-leukocyte aggregates and secreting chemokines at inflamed sites, mainly through the interaction of P-selectin on platelets with PSGL-1 on leukocytes. (Am J Pathol 2010, 176:259-269; DOI: 10.2353/ajpath.2010.081117)