Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence.
Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence.
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DOI：
10.1097/shk.0b013e31821af669
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Lederer JA
中科院分区：
文献类型：
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作者：
O'Leary FM;Tajima G;Delisle AJ;Ikeda K;Dolan SM;Hanschen M;Mannick JA;Lederer JA
烧伤引发增强的炎症状况，称为全身炎症反应综合征（SIRS）或两次打击反应表型。先前的报告表明，巨噬细胞对损伤有反应，并对 Toll 样受体 (TLR) 刺激表现出更高的反应性。由于我们和其他人观察到烧伤小鼠脾脏 GR-1+F4/80+CD11b+ 巨噬细胞显着增加，因此我们希望测试这些巨噬细胞是否可能是显示 LPS 反应性增强的主要巨噬细胞子集。我们在此报告，在体内和离体 LPS 激活后，烧伤促进 GR-1+ 巨噬细胞中较高水平的 TNFα 表达，但不促进 GR-1− 巨噬细胞的表达。接下来我们测试了 CD4+ T 细胞（已知可以抑制损伤诱导的炎症反应）是否可以控制 GR-1+ 巨噬细胞的激活和扩张。有趣的是，我们发现野生型 (WT) 和 CD4 T 细胞缺陷 (CD4−/−) 小鼠之间 GR-1+ 巨噬细胞扩增和 LPS 诱导的 TNFα 表达没有显着差异。然而，进一步的研究表明，LPS 诱导的 TNFα 产生受到 CD4 T 细胞的显着影响。综上所述，这些数据表明 GR-1+F4/80+CD11b+ 巨噬细胞代表了响应烧伤而扩张的初级巨噬细胞亚群，并且 CD4 T 细胞不影响 GR-1+ 巨噬细胞扩张过程，但确实抑制 LPS 诱导的 TNFα 产生。这些数据表明，在严重损伤后调节 GR-1+ 巨噬细胞活化以及 CD4 T 细胞反应可能有助于控制 SIRS 和二次打击反应表型的发展。
Burn injury initiates an enhanced inflammatory condition referred to as the systemic inflammatory response syndrome (SIRS) or the two-hit response phenotype. Prior reports indicated that macrophages respond to injury and demonstrate a heightened reactivity to Toll-like receptor (TLR) stimulation. Since we and others observed a significant increase in splenic GR-1+F4/80+CD11b+ macrophages in burn-injured mice, we wished to test if these macrophages might be the primary macrophage subset that shows heightened LPS reactivity. We report here that burn injury promoted higher level TNFα expression in GR-1+, but not GR-1− macrophages following LPS activation both in vivo and ex vivo. We next tested whether CD4+ T cells, which are known to suppress injury-induced inflammatory responses, might control the activation and expansion of GR-1+ macrophages. Interestingly, we found that GR-1+ macrophage expansion and LPS-induced TNFα expression was not significantly different between wild-type (WT) and CD4 T cell deficient (CD4−/−) mice. However, further investigations showed that LPS-induced TNFα production was significantly influenced by CD4 T cells. Taken together, these data indicate that GR-1+F4/80+CD11b+ macrophages represent the primary macrophage subset that expands in response to burn injury and that CD4 T cells do not influence the GR-1+ macrophage expansion process, but do suppress LPS-induced TNFα production. These data suggest that modulating GR-1+ macrophage activation as well as CD4 T cell responses following severe injury may help control the development of SIRS and the two-hit response phenotype.