Hang L, Haraoka M, Agace W W, Leffler H, Burdick M, Strieter R, Svanborg C
Department of Medical Microbiology, Division of Clinical Immunology, Lund University, Lund, Sweden.
J Immunol. 1999 Mar 1;162(5):3037-44.
IL-8 is a major human neutrophil chemoattractant at mucosal infection sites. This study examined the C-X-C chemokine response to mucosal infection, and, specifically, the role of macrophage inflammatory protein (MIP)-2, one of the mouse IL-8 equivalents, for neutrophil-epithelial interactions. Following intravesical Escherichia coli infection, several C-X-C chemokines were secreted into the urine, but only MIP-2 concentrations correlated to neutrophil numbers. Tissue quantitation demonstrated that kidney MIP-2 production was triggered by infection, and immunohistochemistry identified the kidney epithelium as a main source of MIP-2. Treatment with anti-MIP-2 Ab reduced the urine neutrophil numbers, but the mice had normal tissue neutrophil levels. By immunohistochemistry, the neutrophils were found in aggregates under the pelvic epithelium, but in control mice the neutrophils crossed the urothelium into the urine. The results demonstrate that different chemokines direct neutrophil migration from the bloodstream to the lamina propria and across the epithelium and that MIP-2 serves the latter function. These findings suggest that neutrophils cross epithelial cell barriers in a highly regulated manner in response to chemokines elaborated at this site. This is yet another mechanism that defines the mucosal compartment and differentiates the local from the systemic host response.
白细胞介素-8是黏膜感染部位主要的人类中性粒细胞趋化因子。本研究检测了C-X-C趋化因子对黏膜感染的反应，具体而言，检测了小鼠白细胞介素-8类似物之一巨噬细胞炎性蛋白（MIP）-2在中性粒细胞与上皮细胞相互作用中的作用。膀胱内接种大肠杆菌后，几种C-X-C趋化因子分泌到尿液中，但只有MIP-2的浓度与中性粒细胞数量相关。组织定量分析表明，感染可触发肾脏MIP-2的产生，免疫组织化学鉴定肾脏上皮细胞是MIP-2的主要来源。用抗MIP-2抗体治疗可减少尿液中的中性粒细胞数量，但小鼠组织中的中性粒细胞水平正常。通过免疫组织化学发现，中性粒细胞聚集在盆腔上皮下方，但在对照小鼠中，中性粒细胞穿过尿路上皮进入尿液。结果表明，不同的趋化因子指导中性粒细胞从血液迁移到固有层并穿过上皮，而MIP-2发挥后一种功能。这些发现表明，中性粒细胞以高度受调控的方式响应该部位产生的趋化因子而穿过上皮细胞屏障。这是定义黏膜腔室并区分局部与全身宿主反应的又一机制。
