Luikart Sharon D, Levay-Young Brett, Hinkel Tim, Shearer Jeffry, Mills Charles, Caldwell Michael D, Gyetko Margaret R, Oegema Theodore R
Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.
Wound Repair Regen. 2006 Mar-Apr;14(2):123-8. doi: 10.1111/j.1743-6109.2006.00101.x.
Mactinin, a 31 kDa fragment from the amino-terminal end of alpha-actinin, is chemotactic for monocytes and can promote monocyte/macrophage maturation. Macrophages are essential for wound healing, in which they play key roles in debridement, angiogenesis, fibroblast proliferation, and collagen metabolism. We have previously determined that urokinase is necessary to form mactinin from extracellular alpha-actinin, which may be present at sites of inflammation as a result of cell movement. Thus, urokinase knockout mice are unable to form mactinin and therefore are an ideal model to study mactinin's effects on wound healing. Saline- and mactinin-treated wounds were analyzed in a subcutaneous sponge wound model in both wild-type and urokinase knockout mice. The wounded urokinase knockout mice had markedly decreased leukocyte infiltration compared with wounded wild-type mice. In addition, production of the proinflammatory cytokine, interleukin-12, and of collagen was also decreased in knockouts. Treatment of knockout mice with mactinin resulted in leukocyte infiltration numbers, interleukin-12 levels, and hydroxyproline measurements similar to those in wild-type mice. The results suggest that impaired wound healing in urokinase-deficient mice can be restored by administration of mactinin.
肌动蛋白结合蛋白是α - 辅肌动蛋白氨基末端的一个31 kDa片段，对单核细胞具有趋化作用，并能促进单核细胞/巨噬细胞成熟。巨噬细胞对伤口愈合至关重要，它们在清创、血管生成、成纤维细胞增殖和胶原代谢中发挥关键作用。我们之前已经确定，尿激酶对于从细胞外α - 辅肌动蛋白形成肌动蛋白结合蛋白是必需的，由于细胞移动，细胞外α - 辅肌动蛋白可能存在于炎症部位。因此，尿激酶基因敲除小鼠无法形成肌动蛋白结合蛋白，所以是研究肌动蛋白结合蛋白对伤口愈合影响的理想模型。在野生型和尿激酶基因敲除小鼠的皮下海绵伤口模型中，分析了用生理盐水和肌动蛋白结合蛋白处理的伤口。与受伤的野生型小鼠相比，受伤的尿激酶基因敲除小鼠的白细胞浸润明显减少。此外，基因敲除小鼠中促炎细胞因子白细胞介素 - 12和胶原蛋白的产生也减少。用肌动蛋白结合蛋白治疗基因敲除小鼠后，白细胞浸润数量、白细胞介素 - 12水平和羟脯氨酸测量值与野生型小鼠相似。结果表明，给予肌动蛋白结合蛋白可以恢复尿激酶缺陷小鼠受损的伤口愈合。
