Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1
Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1
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DOI：
10.1172/jci5208
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发表时间：
1999-05-01
影响因子：
15.9
通讯作者：
Kubes, P
中科院分区：
文献类型：
--
作者：
Johnston, B;Burns, AR;Kubes, P
单核细胞趋化蛋白-1（MCP-1）是一种CC趋化因子，当注射到健康动物的组织中时，其刺激单核细胞募集。然而，这种趋化因子在预先存在炎症的模型中的功能尚不清楚。因此，将MCP-1灌注到未处理大鼠或慢性泻药诱导的血管炎大鼠的肠系膜上。与未处理动物相比，MCP-1在免疫大鼠中引起白细胞跨内皮迁移增加。令人惊讶的是，组织学显示，中性粒细胞构成了大部分的白细胞招募免疫动物。在体外，MCP-1也能够诱导中性粒细胞的趋化性分离自免疫大鼠，但不是从幼稚大鼠。流式细胞术揭示了佐剂免疫动物中性粒细胞上CC趋化因子受体CCR 1和CCR 2的新表达。在幼稚动物中，抗CD 18抗体阻断了MCP-1引起的白细胞粘附和迁移。在免疫动物中，抗α（4）-整联蛋白抗体可降低白细胞粘附，但抗CD 18抗体则无此作用。然而，CD 18抗体确实阻断了迁移。据我们所知，这项研究是第一个显示增加的敏感性CC趋化因子的模型与预先存在的炎症，并改变白细胞募集概况响应MCP-1。它还表明，CD 18是所需的趋化因子诱导的白细胞跨内皮迁移，独立于其已知的作用，介导牢固的粘附。
Monocye chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals. However, the function of this chemokine in models with preexisting inflammation is not known. Therefore, MCP-I was superfused over the mesentery of naive rats or rats with chronic adjuvant-induced vasculitis. MCP-I elicited increased leukocyte transendothelial migration in adjuvant-immunized rats compared with naive animals. Surprisingly, histology revealed that neutrophils constituted the majority of leukocytes recruited in adjuvant-immunized animals. In vitro, MCP-1 was also able to induce chemotaxis of neutrophils isolated from adjuvant-immunized rats but not from naive rats. Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals. In naive animals, an antibody against CD18 blocked leukocyte adhesion and emigration in response to MCP-I. In adjuvant-immunized animals, leukocyte adhesion was reduced by antibodies against the alpha(4)-integrin but not by antibodies against CD18. However, the CD18 antibody did block emigration. To our knowledge, this study is the first to show increased sensitivity to a CC chemokine in a model with preexisting inflammation, and altered leukocyte recruitment profiles in response to MCP-1. It also demonstrates that CD18 is required for chemokine-induced leukocyte transendothelial migration, independent of its known role in mediating firm adhesion.