Macrophage colony-stimulating factor accelerates wound healing and upregulates TGF-beta1 mRNA levels through tissue macrophages.
Macrophage colony-stimulating factor accelerates wound healing and upregulates TGF-beta1 mRNA levels through tissue macrophages.
复制标题
DOI：
10.1006/jsre.1997.5178
复制
发表时间：
1997-10
期刊：
影响因子：
--
通讯作者：
L. Wu;Y. Yu;R. Galiano;S. I. Roth;Thomas A. Mustoe, MD, FACS
中科院分区：
文献类型：
--
作者：
L. Wu;Y. Yu;R. Galiano;S. I. Roth;Thomas A. Mustoe, MD, FACS
巨噬细胞集落刺激因子（M-CSF）由参与伤口修复的许多细胞类型产生，但它特异性作用于单核细胞和巨噬细胞。单核细胞源性细胞被认为在伤口愈合中是重要的，但组织巨噬细胞在伤口愈合中的作用的重要性尚未得到很好的定义。在幼兔的正常和缺血耳中制造皮肤溃疡。将rhM-CSF（17微克/伤口）或缓冲液施加到每个伤口。在伤后第7天和第10天将伤口一分为二并进行组织学分析。在所有伤口中测量上皮生长和肉芽组织沉积的量。采用竞争性RT-PCR检测M-CSF处理伤口中TGF-β 1 mRNA水平的增加水平。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）。在非缺血性条件下，rhM-CSF处理的伤口中TGF-β 1 mRNA水平比赋形剂处理的伤口增加5.01倍（N = 8）。相反，在用rhM-CSF处理的缺血性伤口中没有检测到效果，并且当与单独用载体处理的缺血性伤口相比时，这些伤口仅显示TGF-β 1 mRNA水平增加1.66倍。管家基因GAPDH没有变化。由于间充质细胞缺乏M-CSF的受体，用局部rhM-CSF治疗的伤口的改善的愈合必须反映组织巨噬细胞的活化和功能的普遍增强，如通过TGF-β的上调所证明的。在缺血条件下缺乏作用表明，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;这可能表明在细胞水平上伤口愈合受损的发病机制。
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.