Age-related alterations in the inflammatory response to dermal injury
Age-related alterations in the inflammatory response to dermal injury
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DOI：
10.1046/j.0022-202x.2001.01539.x
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发表时间：
2001-11-01
影响因子：
6.5
通讯作者：
DiPietro, LA
中科院分区：
文献类型：
--
作者：
Swift, ME;Burns, AL;DiPietro, LA
先前的研究已证明，伤口愈合能力随年龄增长而下降。尽管许多因素导致了这种与年龄相关的缺陷，但有一个尚未被仔细研究的变量是伤口中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，老年小鼠和年轻小鼠伤口中的中性粒细胞含量相似。相比之下，老年小鼠与年轻小鼠相比，巨噬细胞水平高56%（每平方毫米81±20个细胞对52±13个细胞）。在后期炎症反应中，老年小鼠的伤口在T细胞浸润方面出现延迟，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。尽管有此延迟，老年小鼠伤口中T细胞的最终峰值浓度仍高23%（每平方毫米152±11个细胞对每平方毫米124±21个细胞）。观察到的炎症细胞含量的变化表明，趋化因子的产生可能随年龄而改变。在老年小鼠的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显示，大多数趋化因子，包括MIP - 2、MIP - 1α、MIP - 1β和嗜酸性粒细胞趋化因子的产生往往随年龄下降。由于最佳的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检测。与年轻小鼠相比，老年小鼠伤口中的巨噬细胞吞噬能力降低了37% - 43%。综上所述，数据表明伤口中巨噬细胞和T细胞浸润、趋化因子含量的改变以及伤口巨噬细胞吞噬功能的同时下降都与年龄有关。这些变化可能导致衰老过程中修复反应延迟。
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 mm(2)). 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 2 the wounds of aged mice (152 +/- 11 cells per mm vs 124 +/- 21 cells per mm 2). 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-1 alpha, MIP-1 beta, 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.