Sisco Mark, Chao Jerome D, Kim Injoong, Mogford Jon E, Mayadas Tanya N, Mustoe Thomas A
Wound Healing Research Laboratory, Division of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Wound Repair Regen. 2007 Jul-Aug;15(4):566-71. doi: 10.1111/j.1524-475X.2007.00264.x.
The Mac-1 integrin is an important mediator of migration and inflammatory activation of neutrophils and monocytes. However, the role of Mac-1 in modulating macrophage emigration and activation and its subsequent impact on cutaneous wound healing have not been fully elucidated. To examine the significance of Mac-1 to murine wound healing, we measured epithelialization and granulation tissue formation in partial-thickness ear wounds and full-thickness head wounds, respectively, in Mac-1-deficient mice. Wounds were histologically analyzed at postwounding days 3, 5, and 7. The gap measured between the leading edges of inward-migrating granulation tissue was significantly increased in knockout mice compared with control animals at day 5 (3.8+/-0.3 vs. 2.6+/-0.5 mm; p<0.001) and day 7 (2.2+/-0.4 vs. 0.96+/-0.73 mm; p=0.005). Epithelial gap measurements were also increased in knockout mice vs. wild-type controls at days 3 (0.62+/-0.02 vs. 0.54+/-0.07 mm; p<0.05) and 5 (0.58+/-0.06 vs. 0.39+/-0.08 mm; p<0.001). Immunohistochemistry showed equal numbers of macrophages in knockout and control wounds. These findings show that Mac-1 is required for normal wound healing but that the attenuation in the deposition of granulation tissue and wound epithelialization in Mac-1 knockout mice is not associated with decreased monocyte migration into the wound.
Mac-1整合素是中性粒细胞和单核细胞迁移及炎症激活的重要介质。然而，Mac-1在调节巨噬细胞迁移和激活及其对皮肤伤口愈合的后续影响方面的作用尚未完全阐明。为了研究Mac-1对小鼠伤口愈合的意义，我们分别测量了Mac-1缺陷小鼠耳部分层伤口和头部全层伤口的上皮化和肉芽组织形成情况。在伤后第3、5和7天对伤口进行组织学分析。在第5天（3.8±0.3对2.6±0.5毫米；p<0.001）和第7天（2.2±0.4对0.96±0.73毫米；p=0.005），与对照动物相比，基因敲除小鼠向内迁移的肉芽组织前沿之间的间隙显著增加。在第3天（0.62±0.02对0.54±0.07毫米；p<0.05）和第5天（0.58±0.06对0.39±0.08毫米；p<0.001），基因敲除小鼠的上皮间隙测量值也比野生型对照增加。免疫组织化学显示基因敲除伤口和对照伤口中的巨噬细胞数量相等。这些发现表明，正常伤口愈合需要Mac-1，但Mac-1基因敲除小鼠肉芽组织沉积和伤口上皮化的减弱与单核细胞向伤口的迁移减少无关。
