Inflammationfor Neutrophil Recruitment during Intestinal G Protein-Coupled Receptor 43 Is Essential
Inflammationfor Neutrophil Recruitment during Intestinal G Protein-Coupled Receptor 43 Is Essential
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发表时间：
2009
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通讯作者：
C. Sina;O. Gavrilova;M. Förster;A. Till;S. Derer;F. Hildebrand;Björn Raabe;A. Chalaris;J. Sch
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作者：
C. Sina;O. Gavrilova;M. Förster;A. Till;S. Derer;F. Hildebrand;Björn Raabe;A. Chalaris;J. Sch
分子危险信号将中性粒细胞（多形核白细胞 (PMN)）吸引到感染部位。 G 蛋白偶联受体 (GPR) 43 识别丙酸和丁酸，并在 PMN 上大量表达。 GPR43 激活对于体内免疫反应协调的功能作用尚不清楚。我们检查了野生型和 Gpr43 缺陷小鼠中右旋糖酐硫酸钠 (DSS) 诱导的急性和慢性肠道炎症反应。通过临床体征、组织学评分和细胞因子产生来评估结肠炎症的严重程度。通过 Transwell 细胞趋化测定评估野生型和 Gpr43 缺陷型 PMN 的趋化性。在急性 DSS 结肠炎中观察到中性粒细胞 (PMN) 侵袭减少，并且由于脓毒症并发症导致死亡率增加。在慢性 DSS 结肠炎中，Gpr43 (cid:1) / (cid:1) 动物表现出 PMN 肠道迁移减少，但可防止炎症组织破坏。在无菌炎症模型中未检测到中性粒细胞迁移和细胞因子分泌的显着差异。离体实验表明，GPR43 诱导的迁移依赖于蛋白激酶 p38 (cid:2) 的激活，并且该信号与趋化细胞因子角质形成细胞趋化剂协同作用。有趣的是，Gpr43 小鼠中丙酸和丁酸导致的 L-选择素脱落受到损害。这些结果表明 GPR43 介导的 PMN 募集在抑制肠道细菌易位中发挥着关键作用，同时也强调了 PMN 在介导慢性肠道炎症中组织破坏中的双潜能作用。免疫学杂志，2009，183：7514–7522。
Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43 -deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43 -deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic com-plications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43 (cid:1) / (cid:1) animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38 (cid:2) , and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43 mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation. The Journal of Immunology, 2009, 183: 7514–7522.