Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Immunobiology. 2011 Jul;216(7):753-62. doi: 10.1016/j.imbio.2011.01.001. Epub 2011 Jan 8.
After recruitment to the wound bed, monocytes differentiate into macrophages. Macrophages play a central role in all stages of wound healing and orchestrate the wound healing process. Their functional phenotype is dependent on the wound microenvironment, which changes during healing, hereby altering macrophage phenotype. During the early and short inflammatory phase macrophages exert pro-inflammatory functions like antigen-presenting, phagocytosis and the production of inflammatory cytokines and growth factors that facilitate the wound healing process. As such, the phenotype of wound macrophages in this phase is probably the classically activated or the so-called M1 phenotype. During the proliferative phase, macrophages stimulate proliferation of connective, endothelial and epithelial tissue directly and indirectly. Especially fibroblasts, keratinocytes and endothelial cells are stimulated by macrophages during this phase to induce and complete ECM formation, reepithelialization and neovascularization. Subsequently, macrophages can change the composition of the ECM both during angiogenesis and in the remodelling phase by release of degrading enzymes and by synthesizing ECM molecules. This suggests an important role for alternatively activated macrophages in this phase of wound healing. Pathological functioning of macrophages in the wound healing process can result in derailed wound healing, like the formation of ulcers, chronic wounds, hypertrophic scars and keloids. However, the exact role of macrophages in these processes is still incompletely understood. For treating wound repair disorders more should be elucidated on the role of macrophages in these conditions, especially their functional phenotype, to find more therapeutic opportunities. This review summarizes macrophage function in skin injury repair, thereby providing more insight in macrophage function in wound healing and possible interventions in this process.
招募到创伤床后，单核细胞分化为巨噬细胞。巨噬细胞在伤口愈合的所有阶段都发挥着核心作用，并协调伤口愈合过程。它们的功能表型取决于伤口微环境，而伤口微环境在愈合过程中会发生变化，从而改变巨噬细胞的表型。在早期和短暂的炎症阶段，巨噬细胞发挥促炎功能，如抗原呈递、吞噬作用以及产生炎症细胞因子和生长因子，从而促进伤口愈合过程。因此，这个阶段的伤口巨噬细胞表型可能是经典激活或所谓的 M1 表型。在增殖阶段，巨噬细胞直接和间接地刺激结缔组织、内皮和上皮组织的增殖。特别是在这个阶段，成纤维细胞、角质形成细胞和内皮细胞受到巨噬细胞的刺激，以诱导和完成细胞外基质的形成、再上皮化和新生血管形成。随后，巨噬细胞可以通过释放降解酶和合成 ECM 分子来改变 ECM 的组成，无论是在血管生成还是在重塑阶段。这表明在伤口愈合的这个阶段，交替激活的巨噬细胞具有重要作用。巨噬细胞在伤口愈合过程中的病理性作用可能导致伤口愈合失常，如溃疡、慢性伤口、肥厚性瘢痕和瘢痕疙瘩的形成。然而，巨噬细胞在这些过程中的确切作用仍不完全清楚。为了治疗伤口修复障碍，应该更深入地了解巨噬细胞在这些情况下的作用，特别是它们的功能表型，以寻找更多的治疗机会。这篇综述总结了巨噬细胞在皮肤损伤修复中的作用，从而更深入地了解巨噬细胞在伤口愈合中的作用以及在这个过程中可能的干预措施。
