Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age.
Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age.
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DOI：
10.4049/jimmunol.1201213
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发表时间：
2013-02-15
期刊：
影响因子：
--
通讯作者：
Kovacs EJ
中科院分区：
文献类型：
--
作者：
Brubaker AL;Rendon JL;Ramirez L;Choudhry MA;Kovacs EJ
高龄与先天性和适应性免疫反应的改变有关，这导致老年患者感染风险增加。除了这种免疫功能障碍，老年患者还表现出伤口愈合受损，伤口裂开和慢性伤口的发生率升高。为了评估高龄如何改变宿主对皮肤伤口感染的免疫反应，我们在年轻（3 - 4个月）和老年（18 - 20个月）的BALB/c小鼠中建立了皮肤金黄色葡萄球菌伤口感染的小鼠模型。随着时间推移，与年轻小鼠相比，老年小鼠表现出细菌定植增加和伤口闭合延迟。这些差异并非归因于伤口中性粒细胞或巨噬细胞TLR2或FcγRIII表达的改变，也不是吞噬能力和杀菌活性的年龄相关变化。为了评估趋化性在我们模型中的作用，我们首先在没有伤口损伤的情况下检测了对中性粒细胞趋化因子KC的体内趋化性。在皮下注射KC后，与年轻小鼠相比，老年小鼠在KC剂量增加时招募的中性粒细胞更少。这与我们的伤口感染模型相似，在该模型中，尽管伤口部位的KC、MIP - 2和MCP - 1趋化因子水平相当，但与年轻小鼠相比，老年小鼠的中性粒细胞和巨噬细胞招募减少。这种白细胞积聚减少在早期时间点还与老年小鼠伤口中ICAM - 1水平较低有关。这些由年龄介导的早期中性粒细胞招募缺陷可能改变伤口愈合炎症阶段的动态，影响巨噬细胞招募、细菌清除和伤口闭合。
Advanced age is associated with alterations in innate and adaptive immune responses, which contribute to an increased risk of infection in elderly patients. Coupled with this immune dysfunction, elderly patients demonstrate impaired wound healing with elevated rates of wound dehiscence and chronic wounds. To evaluate how advanced age alters the host immune response to cutaneous wound infection, we developed a murine model of cutaneous Staphylococcus aureus wound infection in young (3–4 month) and aged (18–20 month) BALB/c mice. Aged mice exhibit increased bacterial colonization and delayed wound closure over time compared to young mice. These differences were not attributed to alterations in wound neutrophil or macrophage TLR2 or FcγRIII expression, or age-related changes in phagocytic potential and bactericidal activity. To evaluate the role of chemotaxis in our model, we first examined in vivo chemotaxis in the absence of wound injury to KC, a neutrophil chemokine. In response to a subcutaneous injection of KC, aged mice recruited fewer neutrophils at increasing doses of KC compared to young mice. This paralleled our model of wound infection, where diminished neutrophil and macrophage recruitment was observed in aged mice relative to young mice despite equivalent levels of KC, MIP-2 and MCP-1 chemokine levels at the wound site. This reduced leukocyte accumulation was also associated with lower levels of ICAM-1 in wounds from aged mice at early time points. These age-mediated defects in early neutrophil recruitment may alter the dynamics of the inflammatory phase of wound healing, impacting macrophage recruitment, bacterial clearance and wound closure.
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影响因子：
6.5
作者：
Ashcroft, GS;Horan, MA;Ferguson, MWJ
通讯作者：
Ferguson, MWJ
影响因子：
2.2
作者：
Brubaker, Aleah L.;Schneider, David F.;Kovacs, Elizabeth J.
通讯作者：
Kovacs, Elizabeth J.
影响因子：
2.9
作者：
DiPietro, LA;Reintjes, MG;Gamelli, RL
通讯作者：
Gamelli, RL
影响因子：
5.3
作者：
Boehmer, ED;Meehan, MJ;Kovacs, EJ
通讯作者：
Kovacs, EJ
DOI：
10.1586/edm.10.66
发表时间：
2011-02-01
期刊：
Expert review of dermatology
影响因子：
--
作者：
Brubaker AL;Schneider DF;Kovacs EJ
通讯作者：
Kovacs EJ