CXC chemokine receptor 2 but not C-C chemokine receptor 1 expression is essential for neutrophil recruitment to the cornea in helminth-mediated keratitis (river blindness)
CXC chemokine receptor 2 but not C-C chemokine receptor 1 expression is essential for neutrophil recruitment to the cornea in helminth-mediated keratitis (river blindness)
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DOI：
10.4049/jimmunol.166.6.4035
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发表时间：
2001-03-15
影响因子：
4.4
通讯作者：
Pearlman, E
中科院分区：
文献类型：
--
作者：
Hall, LR;Diaconu, E;Pearlman, E
嗜中性粒细胞和嗜酸性粒细胞浸润到哺乳动物角膜中可导致角膜透明度丧失和严重视力损害。为了鉴定粒细胞募集到角膜基质的介体，我们使用眼盘尾丝虫病（河盲症）的鼠模型确定趋化因子受体CXC趋化因子受体（CXCR）-2（IL-8 R同源物）和CCR 1的相对贡献，其中中性粒细胞和嗜酸性粒细胞向前外周血管迁移到中央角膜，CXCR 2（-/-）和CCR 1（-/-）小鼠经s.c.并将来自寄生蠕虫盘尾丝虫（Onchocerca volvulus）的Ag注射到角膜基质中。我们发现巨噬细胞炎性蛋白（MIP）-2、KC和MIP-1 α的产生定位于角膜基质，而不是上皮，这与中性粒细胞在角膜中的位置一致，CCR 1缺乏并不抑制中性粒细胞或嗜酸性粒细胞向角膜的浸润或角膜混浊的发展。与此形成鲜明对比的是，中性粒细胞向CXCR 2（-/-）小鼠角膜的募集显著受损（与对照BALB/c小鼠相比p < 0.0001），仅在中央角膜中偶尔检测到中性粒细胞。此外，与BALB/c小鼠相比，CXCR 2（-/-）小鼠仅发生轻度角膜混浊。这些差异不是由于CXCR 2（-/-）小鼠角膜基质中KC和MIP-2产生受损所致，这与BALB/c小鼠相似。此外，尽管CXCR 2（-/-）小鼠MIP-1的产生低于BALB/c小鼠，但嗜酸性粒细胞向角膜的募集并未受损。这些观察结果表明CXCR 2表达在中性粒细胞浸润角膜中的关键作用，并可能表明嗜中性粒细胞介导的角膜炎症的免疫干预的目标。
Infiltration of neutrophils and eosinophils into the mammalian cornea can result in loss of corneal clarity and severe visual impairment. To identify mediators of granulocyte recruitment to the corneal stroma, we determined the relative contribution of chemokine receptors CXC chemokine receptor (CXCR)-2 (IL-8R homologue) and CCR1 using a murine model of ocular onchocerciasis (river blindness) in which neutrophils and eosinophils migrate front peripheral vessels to the central cornea, CXCR2(-/-) and CCR1(-/-) mice were immunized s.c. and injected into the corneal stroma with Ags from the parasitic helminth Onchocerca volvulus. We found that production of macrophage-inflammatory protein (MIP)-2, KC, and MIP-la was localized to the corneal stroma, rather than to the epithelium, which was consistent with the location of neutrophils in the cornea, CCR1 deficiency did not inhibit neutrophil or eosinophil infiltration to the cornea or development of corneal opacification. In marked contrast, neutrophil recruitment to the corneas of CXCR2(-/-) mice was significantly impaired (p < 0.0001 compared with control, BALB/c mice) with only occasional neutrophils detected in the central cornea. Furthermore, CXCR2(-/-) mice developed only mild corneal opacification compared with BALB/c mice. These differences were not due to impaired KC and MIP-2 production in the corneal stroma of CXCR2(-/-) mice, which was similar to BALB/c mice. Furthermore, although MIP-1 production was lower in CXCR2(-/-) mice than BALB/c mice, eosinophil recruitment to the cornea was not impaired. These observations demonstrate the critical role for CXCR2 expression in neutrophil infiltration to the cornea and may indicate a target for immune intervention in neutrophil-mediated corneal inflammation.