Yamamoto Hideaki, Nagata Makoto, Sakamoto Yoshio
Keiyo Clinic of Internal Medicine, Chiba, Japan.
Ann Allergy Asthma Immunol. 2005 Feb;94(2):292-300. doi: 10.1016/S1081-1206(10)61311-7.
Interaction between eosinophil alpha4 integrin and vascular cell adhesion molecule 1 (VCAM-1) expressed on activated endothelial cells may be a key step in the selective recruitment of eosinophils from the circulation to sites of inflammation.
To investigate the factor(s) that induces transmigration of eosinophils after firm adhesion via the alpha4 integrin/VCAM-1 pathway.
We examined the effects of a variety of inflammatory mediators on the migration of eosinophils across recombinant human (rh) intracellular adhesion molecule 1- or rhVCAM-1-coated Transwell filters or VCAM-1-expressing human pulmonary microvascular endothelial cells (HPMECs) that had been stimulated with interleukin 4 (IL-4) and tumor necrosis factor alpha. The number of eosinophils that had transmigrated was evaluated by measuring eosinophil peroxidase activity.
The CC chemokines RANTES (regulated on activation, normal T-cell expressed, and secreted), eotaxin, eotaxin 2, monocyte chemotactic protein 3 (MCP-3), and MCP-4 each increased eosinophil transmigration across rhVCAM-1-coated filters compared with fetal calf serum-blocked or rh intracellular adhesion molecule 1-coated filters (P < .01). On the other hand, platelet-activating factor, C5a, formyl-methionyl-leucil-phenylalanine, granulocyte-macrophage colony-stimulating factor, IL-5, and IL-8 did not enhance migration across rhVCAM-1. The enhancement of migration by RANTES in the presence of rhVCAM-1 was blocked by an anti-alpha4 integrin monoclonal antibody. CC chemokines augmented eosinophil transmigration across VCAM-1-expressing HPMECs compared with resting HPMECs (P < .01). Conversely, the transmigration induced by platelet-activating factor, C5a, formyl-methionyl-leucil-phenylalanine, or IL-8 was not modified by the expression of VCAM-1 on HPMECs.
CC chemokines induce transendothelial migration of eosinophils after interaction between eosinophil alpha4 integrin and endothelial VCAM-1.
嗜酸性粒细胞α4整合素与活化内皮细胞上表达的血管细胞黏附分子1（VCAM-1）之间的相互作用可能是嗜酸性粒细胞从循环中选择性募集至炎症部位的关键步骤。
研究通过α4整合素/VCAM-1途径牢固黏附后诱导嗜酸性粒细胞跨内皮迁移的因素。
我们检测了多种炎症介质对嗜酸性粒细胞跨重组人（rh）细胞间黏附分子1或rhVCAM-1包被的Transwell滤膜，或经白细胞介素4（IL-4）和肿瘤坏死因子α刺激的表达VCAM-1的人肺微血管内皮细胞（HPMECs）迁移的影响。通过测量嗜酸性粒细胞过氧化物酶活性评估迁移的嗜酸性粒细胞数量。
与胎牛血清封闭或rh细胞间黏附分子1包被的滤膜相比，CC趋化因子RANTES（活化调节、正常T细胞表达和分泌）、嗜酸性粒细胞趋化因子、嗜酸性粒细胞趋化因子2、单核细胞趋化蛋白3（MCP-3）和MCP-4均增加了嗜酸性粒细胞跨rhVCAM-1包被滤膜的迁移（P <.01）。另一方面，血小板活化因子、C5a、甲酰甲硫氨酰亮氨酰苯丙氨酸、粒细胞-巨噬细胞集落刺激因子、IL-5和IL-8并未增强跨rhVCAM-1的迁移。抗α4整合素单克隆抗体可阻断RANTES在rhVCAM-1存在时对迁移的增强作用。与静息HPMECs相比，CC趋化因子增加了嗜酸性粒细胞跨表达VCAM-1的HPMECs的迁移（P <.01）。相反，血小板活化因子、C5a、甲酰甲硫氨酰亮氨酰苯丙氨酸或IL-8诱导的迁移并未因HPMECs上VCAM-1的表达而改变。
CC趋化因子在嗜酸性粒细胞α4整合素与内皮VCAM-1相互作用后诱导嗜酸性粒细胞跨内皮迁移。
