The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury
The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury
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DOI：
10.1038/cmi.2011.8
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发表时间：
2011-07-01
影响因子：
24.1
通讯作者：
Kaku, Mitsuo
中科院分区：
文献类型：
--
作者：
Yamada, Mitsuhiro;Kubo, Hiroshi;Kaku, Mitsuo
炎症刺激物，如微生物或脂多糖，诱导中性粒细胞从骨髓中快速释放，并促进中性粒细胞迁移到炎症部位，以促进宿主防御。然而，中性粒细胞在炎症组织中的过度积累和保留可在炎症的后期阶段引起严重的组织损伤。最近的研究报道，在损伤的肺中CXCL 12水平和其受体CXCR 4在损伤的肺中积聚的中性粒细胞上均增加;此外，这些研究表明，CXCL 12/CXCR 4信号通路参与了脂多糖（LPS）诱导的肺损伤的后期阶段的中性粒细胞积聚。然而，中性粒细胞表面CXCR 4表达增加的机制尚不清楚。在这项研究中，我们发现，在LPS诱导的肺损伤模型小鼠的肺血管外，但不是血管内，中性粒细胞表面CXCR 4的表达增加。此外，离体研究表明，CXCL 12不仅作为一种化学引诱物，而且作为一种抑制剂的细胞死亡的肺中性粒细胞表达CXCR 4。硫脂，L-选择素的天然配体之一，诱导分离的循环中性粒细胞表面CXCR 4表达的增加，表明L-选择素的活化可能参与表面CXCR 4的增加。我们的研究结果表明，中性粒细胞表面CXCR 4水平增加后外渗到受伤的肺，可能通过激活L-选择素。CXCL 12/CXCR 4信号通路在急性肺损伤期间调节中性粒细胞活性中起重要作用，不仅通过促进趋化性，而且通过抑制细胞死亡。Cellular & Molecular Immunology（2011）8，305-314; doi：10.1038/cmi.2011.8; 2011年4月4日在线发表
Inflammatory stimuli, such as a microbes or lipopolysaccharides, induce a rapid release of neutrophils from the bone marrow and promote neutrophil migration into inflamed sites to promote host defense. However, an excess accumulation and retention of neutrophils in inflamed tissue can cause severe tissue injuries in the later stages of inflammation. Recent studies have reported that both CXCL12 levels in injured lungs and its receptor, CXCR4, on accumulated neutrophils in injured lungs, increased; furthermore, these studies showed that the CXCL12/CXCR4 signaling pathway participated in neutrophil accumulation in the later stages of lipopolysaccharide (LPS)-induced lung injury. However, the mechanisms underlying this increase in surface CXCR4 expression in neutrophils remain unclear. In this study, we found that surface CXCR4 expression increased in extravascular, but not intravascular, neutrophils in the lungs of LPS-induced lung injury model mice. Furthermore, ex vivo studies revealed that CXCL12 acted not only as a chemoattractant, but also as a suppressor of cell death for the lung neutrophils expressing CXCR4. Sulfatide, one of the native ligands for L-selectin, induced the increase of surface CXCR4 expression on isolated circulating neutrophils, suggesting that the activation of L-selectin may be involved in the increase in surface CXCR4. Our findings show that surface CXCR4 levels on neutrophils increase after extravasation into injured lungs, possibly through the activation of L-selectin. The CXCL12/CXCR4 signaling pathway plays an important role in the modulation of neutrophil activity during acute lung injury, not only by promoting chemotaxis but also by suppressing cell death. Cellular & Molecular Immunology (2011) 8, 305-314; doi: 10.1038/cmi.2011.8; published online 4 April 2011