Department of Periodontics, Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
Brain Behav Immun. 2013 Feb;28:207-17. doi: 10.1016/j.bbi.2012.07.013. Epub 2012 Aug 3.
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.
先前的研究报告指出，压力会延迟伤口愈合、损害细菌清除能力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伤口部位的细菌。这些细胞的适当招募和功能对于有效清除细菌是必要的。在我们目前的研究中，我们发现束缚应激会导致中性粒细胞过度募集，延长愈合的炎症期，并诱导中性粒细胞趋化因子 MIP-2 和 KC 的基因表达。然而，束缚应激并不影响巨噬细胞的浸润。应激会降低吞噬细胞的体外吞噬能力，但不会影响超氧化物的产生。应激小鼠外周血单核细胞表面的黏附分子 CD11b 和 TLR4 表达减少。伤口部位巨噬细胞的表型也发生了改变。促炎经典激活型巨噬细胞标记物 CXCL10 和 CCL5 的基因表达下调；与伤口愈合相关的巨噬细胞标记物 CCL22、IGF-1、RELMα；以及调节性巨噬细胞标记物趋化因子 CCL1 的基因表达也下调。束缚应激还诱导了 IL10 基因表达的上调。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，束缚应激抑制了巨噬细胞群体的表型转变，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。调节巨噬细胞表型可能为临床应激条件下治疗伤口提供一种新的治疗方法。
