Wu L, Yu Y L, Galiano R D, Roth S I, Mustoe T A
Division of Plastic Surgery, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J Surg Res. 1997 Oct;72(2):162-9. doi: 10.1006/jsre.1997.5178.
Macrophage colony-stimulating factor (M-CSF) is produced by many cell types involved in wound repair, yet it acts specifically on monocytes and macrophages. The monocyte-derived cell is thought to be important in wound healing, but the importance of the role of tissue macrophages in wound healing has not been well defined. Dermal ulcers were created in normal and ischemic ears of young rabbits. Either rhM-CSF (17 microg/wound) or buffer was applied to each wound. Wounds were bisected and analyzed histologically at Days 7 and 10 postwounding. The amounts of epithelial growth and granulation tissue deposition were measured in all wounds. The level of increase of TGF-beta1 mRNA level in M-CSF-treated wounds was examined using competitive RT-PCR. M-CSF increased new granulation tissue formation by 37% (N = 21, P < 0.01) and 50% (P < 0.01) after single and multiple treatments, respectively, in nonischemic wounds. TGF-beta1 mRNA levels in rhM-CSF-treated wounds increased 5.01-fold (N = 8) over vehicle-treated wounds under nonischemic conditions. In contrast, no effect could be detected in ischemic wounds treated with rhM-CSF, and these wounds only showed a 1.66-fold increase in TGF-beta1 mRNA levels when compared to ischemic wounds treated with vehicle alone. GAPDH, a housekeeping gene, showed no change. As mesenchymal cells lack receptors for M-CSF, the improved healing of wounds treated with topical rhM-CSF must reflect a generalized enhancement of activation and function of tissue macrophages, as demonstrated by upregulation of TGF-beta. The lack of effect under ischemic conditions suggests that either macrophage activity and/or response to M-CSF is adversely affected under those conditions; this may suggest the pathogenesis of impaired wound healing at the cellular level.
巨噬细胞集落刺激因子（M-CSF）由许多参与伤口修复的细胞类型产生，但它特异性作用于单核细胞和巨噬细胞。单核细胞衍生细胞被认为在伤口愈合中很重要，但组织巨噬细胞在伤口愈合中的作用重要性尚未得到很好的界定。在年轻兔子的正常耳朵和缺血耳朵上制造皮肤溃疡。将重组人M-CSF（17微克/伤口）或缓冲液应用于每个伤口。在受伤后第7天和第10天，将伤口一分为二并进行组织学分析。测量所有伤口上皮生长和肉芽组织沉积的量。使用竞争性逆转录聚合酶链反应检测M-CSF处理伤口中转化生长因子β1（TGF-β1）mRNA水平的增加程度。在非缺血性伤口中，单次和多次治疗后，M-CSF分别使新肉芽组织形成增加37%（N = 21，P < 0.01）和50%（P < 0.01）。在非缺血条件下，重组人M-CSF处理伤口中的TGF-β1 mRNA水平比载体处理伤口增加了5.01倍（N = 8）。相比之下，重组人M-CSF处理的缺血性伤口未检测到效果，与仅用载体处理的缺血性伤口相比，这些伤口的TGF-β1 mRNA水平仅增加了1.66倍。管家基因甘油醛-3-磷酸脱氢酶（GAPDH）无变化。由于间充质细胞缺乏M-CSF受体，局部应用重组人M-CSF治疗的伤口愈合改善一定反映了组织巨噬细胞激活和功能的普遍增强，如TGF-β上调所示。缺血条件下缺乏效果表明，在这些条件下巨噬细胞活性和/或对M-CSF的反应受到不利影响；这可能提示了细胞水平伤口愈合受损的发病机制。
