Avniel Shani, Arik Zaretski, Maly Alex, Sagie Assa, Basst Hanna Ben, Yahana Merav Darash, Weiss Ido D, Pal Boaz, Wald Ori, Ad-El Dean, Fujii Nobutaka, Arenzana-Seisdedos Fernando, Jung Steffen, Galun Eithan, Gur Eyal, Peled Amnon
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
J Invest Dermatol. 2006 Feb;126(2):468-76. doi: 10.1038/sj.jid.5700069.
Burn wound healing is a complex process consisting of an inflammatory phase, the formation of granulation tissue, and remodeling. The role of the CXCL12/CXCR4 pathway in the recovery of skin following burns is unknown. We found that CXCL12 is similarly expressed in human, swine, and rat skin by pericyte and endothelial cells, fibrous sheet, fibroblasts, and axons. Following burns, the levels of CXCL12 were markedly increased in human burn blister fluids. One day after injury, there was a gradual increase in the expression of CXCL12 in the hair follicles and in blood vessel endothelium surrounding the burn. Three to 11 days following burns, an increased number of fibroblasts expressing CXCL12 were observed in the recovering dermis of rat, swine, and human skin. In contrast to CXCL12, CXCR4 expression was detected in proliferating epithelial cells as well as in eosinophils and mononuclear cells infiltrating the skin. In vitro, CXCL12 was expressed by primary human skin fibroblasts, but not by keratinocytes, and was stimulated by wounding a confluent cell layer of these fibroblasts. Blocking the CXCR4/CXCL12 axis resulted in the significant reduction in eosinophil accumulation in the dermis and improved epithelialization. Thus, blocking CXCR4/CXCL12 interaction may significantly improve skin recovery after burns.
烧伤创面愈合是一个复杂的过程，包括炎症期、肉芽组织形成和重塑。CXCL12/CXCR4通路在烧伤后皮肤恢复中的作用尚不清楚。我们发现，CXCL12在人、猪和大鼠皮肤的周细胞、内皮细胞、纤维片、成纤维细胞和轴突中表达相似。烧伤后，人烧伤水疱液中CXCL12水平显著升高。受伤后一天，毛囊和烧伤周围血管内皮中CXCL12的表达逐渐增加。烧伤后3至11天，在大鼠、猪和人皮肤的愈合真皮中观察到表达CXCL12的成纤维细胞数量增加。与CXCL12不同，CXCR4在增殖的上皮细胞以及浸润皮肤的嗜酸性粒细胞和单核细胞中被检测到。在体外，原代人皮肤成纤维细胞表达CXCL12，而角质形成细胞不表达，并且通过损伤这些成纤维细胞的汇合细胞层来刺激CXCL12的表达。阻断CXCR4/CXCL12轴导致真皮中嗜酸性粒细胞积聚显著减少，并改善上皮形成。因此，阻断CXCR4/CXCL12相互作用可能显著改善烧伤后的皮肤恢复。
