Injury Is a Major Inducer of Epidermal Innate Immune Responses during Wound Healing
Injury Is a Major Inducer of Epidermal Innate Immune Responses during Wound Healing
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DOI：
10.1038/jid.2009.284
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发表时间：
2010-04-01
影响因子：
6.5
通讯作者：
Sorensen, Ole E.
中科院分区：
文献类型：
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作者：
Roupe, K. Markus;Nybo, Mads;Sorensen, Ole E.
我们研究了损伤对人类皮肤创伤的表皮先天免疫反应的重要性。我们发现，由于IL-8的产生，损伤独立于浸润性炎症细胞，在损伤皮肤中对中性粒细胞产生显著的趋化活性。此外，损伤是皮肤创伤中抗菌多肽(AMPs)表达的主要诱因。在人类皮肤中，这些损伤诱导的先天免疫反应是通过激活表皮生长因子受体(EGFR)来介导的。因此，抑制EGFR既阻止了损伤皮肤产生的趋化活性，也阻止了大多数AMP的表达。损伤的重要性在小鼠体内实验中得到了证实，在这些实验中，与感染无关的损伤是皮肤伤口中AMPS的有效诱因。据我们所知，这些数据提供了以前未报道的损伤和中性粒细胞聚集之间的分子联系，并确定了创伤表皮中IL-8和AMPs大量表达的分子背景。从概念上讲，这些数据表明，创伤引起的生长因子反应对于中性粒细胞在皮肤伤口中的募集是重要的。
We examined the importance of injury for the epidermal innate immune response in human skin wounds. We found that injury, independent of infiltrating inflammatory cells, generated prominent chemotactic activity toward neutrophils in injured skin because of IL-8 production. Furthermore, injury was a major inducer of the expression of antimicrobial (poly)peptides (AMPs) in skin wounds. In human skin, these injury-induced innate immune responses were mediated by activation of the epidermal growth factor receptor (EGFR). Consequently, inhibition of the EGFR blocked both the chemotactic activity generated in injured skin and the expression of the majority of the AMPs. The importance of injury was confirmed in mouse experiments in vivo, in which injury independent of infection was a potent inducer of AMPs in skin wounds. To our knowledge, these data thereby provide a previously unreported molecular link between injury and neutrophil accumulation and identify the molecular background for the vast expression of IL-8 and AMPs in wounded epidermis. Conceptually, these data show that the growth factor response elicited by injury is important for the recruitment of neutrophils in skin wounds.