Restraint stress alters neutrophil and macrophage phenotypes during wound healing.
Restraint stress alters neutrophil and macrophage phenotypes during wound healing.
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DOI：
10.1016/j.bbi.2012.07.013
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发表时间：
2013-02
影响因子：
15.1
通讯作者：
Marucha, Phillip T.
中科院分区：
文献类型：
--
作者：
Tymen, Stephanie D.;Rojas, Isolde G.;Zhou, Xiaofeng;Fang, Zong Juan;Zhao, Yan;Marucha, Phillip T.
先前的研究报道，应激延迟伤口愈合，损害细菌清除，并增加机会性感染的风险。中性粒细胞和巨噬细胞负责清除存在于伤口部位的细菌。这些细胞的适当募集和功能是有效清除细菌所必需的。在我们目前的研究中，我们发现抑制应激诱导了中性粒细胞的过度募集，延长了愈合的炎症期，中性粒细胞吸引趋化因子MIP-2和KC的基因表达，但抑制应激不影响巨噬细胞的浸润。应激降低了体外吞噬细胞的吞噬能力，但不影响超氧化物的产生。应激小鼠外周血单核细胞表面粘附分子CD11b和TLR4表达降低。出现在伤口部位的巨噬细胞表型也发生了改变。促炎经典活化巨噬细胞标志物CXCL10、CCL5基因表达下调；与伤口愈合巨噬细胞相关的标志物，CCL22, IGF-1, RELMα；以及调节性巨噬细胞标记物趋化因子CCL1。抑制应激也诱导IL10基因表达上调。总之，我们的研究表明，与正常伤口愈合过程中观察到的变化相比，抑制应激抑制巨噬细胞群的表型转移，而巨噬细胞的数量保持不变。我们还观察到趋化因子基因表达的普遍抑制。巨噬细胞表型的调节可以为临床应激条件下伤口的治疗提供一种新的治疗方法。
Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting.
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影响因子：
15.1
作者：
Curtin, Niamh M.;Mills, Kingston H. G.;Connor, Thomas J.
通讯作者：
Connor, Thomas J.
影响因子：
15.1
作者：
Horan, MP;Quan, N;Marucha, PT
通讯作者：
Marucha, PT
影响因子：
20.3
作者：
Ehrchen, Jan;Steinmueller, Lars;Roth, Johannes
通讯作者：
Roth, Johannes
DOI：
10.1152/ajplung.2001.280.1.l58
发表时间：
2001-01-01
影响因子：
4.9
作者：
Maus, U;Herold, S;Lohmeyer, J
通讯作者：
Lohmeyer, J
影响因子：
3.8
作者：
Mirza, Rita;Koh, Timothy J.
通讯作者：
Koh, Timothy J.