Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Sendai, Japan.
Wound Repair Regen. 2011 Sep-Oct;19(5):608-21. doi: 10.1111/j.1524-475X.2011.00721.x.
Wound healing is promoted by the presence of replicating microorganisms adhering to the wounded tissue, but the precise mechanism is not fully understood. In the present study, using a rat model with full-thickness dermal wounds, we examined the effect of Pseudomonas aeruginosa inoculation on wound healing and the role of neutrophils infiltrating the wound site. Within 3 days, inoculation with this bacterium had accelerated re-epithelialization, epidermal cell proliferation, and neo-vascularization, as well as the local infiltration of neutrophils, which reached a peak at 24 hours. Tumor necrosis factor (TNF)-α was detected in the wound tissues on the mRNA and protein levels within 24 hours. Flow cytometry and immunohistochemical analyses detected higher levels of TNF-α in the infiltrating neutrophils in rats inoculated with P. aeruginosa than in uninoculated rats. Neutropenic rats treated with anti-neutrophil mAb or cyclophosphamide exhibited significant attenuation in re-epithelialization, epidermal cell proliferation, neo-vascularization, and TNF-α synthesis compared with control; administration of TNF-α reversed these attenuations. These wound-healing responses were decelerated in rats treated with anti-TNF-α mAb, as was the infiltration of neutrophils. These results indicate that inoculation with P. aeruginosa promotes wound healing by inducing the infiltration of neutrophils, which play a critical role as a major source of TNF-α.
创伤愈合是由附着在创伤组织上的复制微生物的存在所促进的，但确切的机制尚未完全理解。在本研究中，我们使用全层皮肤创伤的大鼠模型，研究了铜绿假单胞菌接种对创伤愈合的影响以及浸润创伤部位的中性粒细胞的作用。在 3 天内，这种细菌的接种加速了再上皮化、表皮细胞增殖和新血管形成，以及中性粒细胞的局部浸润，在 24 小时达到高峰。在接种后 24 小时内，伤口组织中 TNF-α 在 mRNA 和蛋白质水平上均有检测到。流式细胞术和免疫组织化学分析检测到，在接种铜绿假单胞菌的大鼠中，浸润中性粒细胞中的 TNF-α 水平高于未接种大鼠。与对照相比，用抗中性粒细胞 mAb 或环磷酰胺处理的中性粒细胞减少大鼠的再上皮化、表皮细胞增殖、新血管形成和 TNF-α 合成明显减弱；给予 TNF-α 可逆转这些减弱。在接受抗 TNF-α mAb 治疗的大鼠中，这些伤口愈合反应以及中性粒细胞的浸润均减慢。这些结果表明，铜绿假单胞菌的接种通过诱导中性粒细胞的浸润来促进伤口愈合，而中性粒细胞作为 TNF-α 的主要来源起着关键作用。
