Martin Paul, D'Souza Deana, Martin Julie, Grose Richard, Cooper Lisa, Maki Rich, McKercher Scott R
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Curr Biol. 2003 Jul 1;13(13):1122-8. doi: 10.1016/s0960-9822(03)00396-8.
Damage to neonatal and adult tissues always incites an influx of inflammatory neutrophils and macrophages. Besides clearing the wound of invading microbes, these cells are believed to be crucial coordinators of the repair process, acting both as professional phagocytes to clear wound debris and as a major source of wound growth factor signals. Here we report wound healing studies in the PU.1 null mouse, which is genetically incapable of raising the standard inflammatory response because it lacks macrophages and functioning neutrophils. Contrary to dogma, we show that these "macrophageless" mice are able to repair skin wounds with similar time course to wild-type siblings, and that repair appears scar-free as in the embryo, which also heals wounds without raising an inflammatory response. The growth factor and cytokine profile at the wound site is changed, cell death is reduced, and dying cells are instead engulfed by stand-in phagocytic fibroblasts. We also show that hyperinnervation of the wound site, previously believed to be a consequence of inflammation, is present in the PU.1 null wound, too.
新生儿和成年组织的损伤总会引发炎性中性粒细胞和巨噬细胞的大量涌入。除了清除伤口处入侵的微生物外，这些细胞被认为是修复过程的关键协调者，它们既是清除伤口碎片的专业吞噬细胞，也是伤口生长因子信号的主要来源。在此，我们报告了在PU.1基因敲除小鼠身上进行的伤口愈合研究，该小鼠由于缺乏巨噬细胞和有功能的中性粒细胞，在基因上无法引发标准的炎症反应。与传统观念相反，我们发现这些“无巨噬细胞”小鼠能够以与野生型同窝小鼠相似的时间进程修复皮肤伤口，并且修复过程似乎像胚胎一样无疤痕，胚胎愈合伤口时也不会引发炎症反应。伤口部位的生长因子和细胞因子谱发生了变化，细胞死亡减少，死亡细胞反而被替代的吞噬性成纤维细胞吞噬。我们还表明，伤口部位的神经支配过度（以前认为是炎症的结果）在PU.1基因敲除小鼠的伤口中也存在。
