Program of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
J Immunol. 2012 Jan 15;188(2):844-53. doi: 10.4049/jimmunol.1101736. Epub 2011 Dec 7.
Neutrophil (polymorphonuclear leukocytes [PMN]) infiltration plays a central role in inflammation and is also a major cause of tissue damage. Thus, PMN infiltration must be tightly controlled. Using zymosan-induced peritonitis as an in vivo PMN infiltration model, we show in this study that PMN response and infiltration were significantly enhanced in mice experiencing various types of systemic inflammation, including colitis and diabetes. Adoptive transfer of leukocytes from mice with inflammation into healthy recipients or from healthy into inflammatory recipients followed by inducing peritonitis demonstrated that both circulating PMN and tissue macrophages were altered under inflammatory conditions and that they collectively contributed to enhanced PMN infiltration. Detailed analyses of dextran sulfate sodium-elicited colitis revealed that enhancement of PMN infiltration and macrophage function occurred only at the postacute/chronic phase of inflammation and was associated with markedly increased IL-17A in serum. In vitro and ex vivo treatment of isolated PMN and macrophages confirmed that IL-17A directly modulates these cells and significantly enhances their inflammatory responses. Neutralization of IL-17A eliminated the enhancement of PMN infiltration and IL-6 production and also prevented severe tissue damage in dextran sulfate sodium-treated mice. Thus, IL-17A produced at the chronic stage of colitis serves as an essential feedback signal that enhances PMN infiltration and promotes inflammation.
中性粒细胞（多形核白细胞[PMN]）浸润在炎症中起着核心作用，也是组织损伤的主要原因。因此，PMN 浸润必须得到严格控制。本研究采用酵母聚糖诱导的腹膜炎作为体内 PMN 浸润模型，结果表明，患有各种系统性炎症（包括结肠炎和糖尿病）的小鼠的 PMN 反应和浸润显著增强。将来自炎症小鼠的白细胞或来自健康小鼠的白细胞过继转移到健康接受者或炎症接受者体内，然后诱导腹膜炎，结果表明，在炎症条件下循环 PMN 和组织巨噬细胞发生改变，它们共同导致 PMN 浸润增强。详细分析葡聚糖硫酸钠诱导的结肠炎发现，PMN 浸润和巨噬细胞功能的增强仅发生在炎症的亚急性期/慢性期，并且与血清中明显增加的白细胞介素 17A（IL-17A）相关。对分离的 PMN 和巨噬细胞进行的体外和离体处理证实，IL-17A 直接调节这些细胞，并显著增强它们的炎症反应。IL-17A 的中和消除了 PMN 浸润和白细胞介素 6（IL-6）产生的增强，并防止了葡聚糖硫酸钠处理的小鼠的严重组织损伤。因此，结肠炎慢性期产生的白细胞介素 17A 作为一种必需的反馈信号，增强 PMN 浸润并促进炎症。
