Swift M E, Burns A L, Gray K L, DiPietro L A
Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA.
J Invest Dermatol. 2001 Nov;117(5):1027-35. doi: 10.1046/j.0022-202x.2001.01539.x.
Previous studies have documented that the ability to heal wounds declines with age. Although many factors contribute to this age-associated deficit, one variable that has not been carefully examined is leukocyte recruitment and function in wounds. This investigation compares the inflammatory response in excisional wounds of young (age 8 wk) and aged (age 22 mo) mice. In the early inflammatory response, neutrophil content of wounds was similar for both aged and young mice. In contrast, macrophage levels were 56% higher in aged versus young mice (81 +/- 20 vs 52 +/- 13 cells per mm2). In the later inflammatory response, wounds of aged mice exhibited a delay in T cell infiltration, with maximum T cell levels at day 10 in aged mice versus day 7 in young mice. Despite this delay, the eventual peak concentration of T cells was 23% higher in the wounds of aged mice (152 +/- 11 cells per mm2 vs 124 +/- 21cells per mm2). The observed alterations in inflammatory cell content suggested that chemokine production might be altered with age. An elevation of monocyte chemoattractant protein (MCP-1) levels was observed in wounds of aged mice. RNase protection studies, however, revealed that the production of most chemokines, including MIP-2, MIP-1alpha, MIP-1beta, and eotaxin, tended to decline with age. Because optimal wound healing requires both appropriate macrophage infiltration and phagocytic activity, phagocytosis was examined. Compared to young mice, wound macrophages from aged mice exhibited a 37%-43% reduction in phagocytic capacity. Taken together, the data demonstrate age-related shifts in both macrophage and T cell infiltration into wounds, alterations in chemokine content, and a concurrent decline in wound macrophage phagocytic function. These alterations may contribute to the delayed repair response of aging.
以往的研究表明，伤口愈合能力会随着年龄的增长而下降。尽管有许多因素导致了这种与年龄相关的缺陷，但一个尚未得到仔细研究的变量是伤口处白细胞的募集和功能。本研究比较了年轻（8周龄）和老年（22月龄）小鼠切除伤口的炎症反应。在早期炎症反应中，老年和年轻小鼠伤口中的中性粒细胞含量相似。相比之下，老年小鼠伤口中的巨噬细胞水平比年轻小鼠高56%（分别为每平方毫米81±20个细胞和52±13个细胞）。在后期炎症反应中，老年小鼠伤口的T细胞浸润出现延迟，老年小鼠在第10天达到T细胞水平峰值，而年轻小鼠在第7天达到峰值。尽管存在这种延迟，但老年小鼠伤口中T细胞的最终峰值浓度比年轻小鼠高23%（分别为每平方毫米152±11个细胞和124±21个细胞）。观察到的炎症细胞含量变化表明，趋化因子的产生可能会随着年龄的增长而改变。在老年小鼠伤口中观察到单核细胞趋化蛋白（MCP-1）水平升高。然而，核糖核酸酶保护研究表明，包括MIP-2、MIP-1α、MIP-1β和嗜酸性粒细胞趋化因子在内的大多数趋化因子的产生往往会随着年龄的增长而下降。由于最佳伤口愈合需要适当的巨噬细胞浸润和吞噬活性，因此对吞噬作用进行了研究。与年轻小鼠相比，老年小鼠伤口巨噬细胞的吞噬能力降低了37%-43%。综上所述，数据表明巨噬细胞和T细胞向伤口浸润存在与年龄相关的变化、趋化因子含量改变以及伤口巨噬细胞吞噬功能同时下降。这些改变可能导致衰老过程中修复反应延迟。
