Differential Roles of Macrophages in Diverse Phases of Skin Repair
Differential Roles of Macrophages in Diverse Phases of Skin Repair
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DOI：
10.4049/jimmunol.0903356
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
Eming, Sabine A.
中科院分区：
文献类型：
--
作者：
Lucas, Tina;Waisman, Ari;Eming, Sabine A.
巨噬细胞的流入在组织修复中起着至关重要的作用。然而，由于巨噬细胞在组织损伤和修复中具有双重功能，其在愈合反应过程中的确切作用一直是争论的焦点。我们验证了这样一个假设：在机械性损伤后的皮肤修复不同阶段所招募的巨噬细胞发挥特定功能以恢复组织完整性。为此，我们建立了一个小鼠模型，该模型能够在修复反应的连续阶段有条件地清除巨噬细胞。在修复反应早期（炎症期）限制清除巨噬细胞会显著减少血管化肉芽组织的形成，阻碍上皮化，并导致瘢痕形成最小化。相反，在修复反应的连续中期（组织形成期）限制清除巨噬细胞会导致伤口组织严重出血。在这些情况下，不会过渡到随后的组织成熟和伤口闭合阶段。最后，在修复后期（组织成熟期）限制清除巨噬细胞并不会对修复反应的结果产生显著影响。这些结果表明，巨噬细胞在皮肤修复的不同阶段发挥不同的功能，这对于控制修复事件的自然顺序至关重要。《免疫学杂志》，2010年，184卷：3964 - 3977页
Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events. The Journal of Immunology, 2010, 184: 3964-3977.