Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Neuroimmunomodulation. 2010;17(2):79-87. doi: 10.1159/000258690. Epub 2009 Nov 17.
Stress can alter many aspects of the immune response, and many studies have been conducted on the effects of stress on inflammatory processes, but little is known about its influence on the resolution of inflammation in tissue homeostasis, which includes the clearance of apoptotic cells by macrophages in a non-phlogistic way. In the present study, we investigated the effect of acute cold stress on the phagocytosis of apoptotic cells by macrophages.
Mice were submitted to acute cold stress (4 degrees C for 4 h) and the capacity of peritoneal macrophages to phagocyte apoptotic thymocytes and to secrete anti-inflammatory cytokines was evaluated. Plasma corticosterone and catecholamine levels were investigated to assess their effect on the phagocytic capacity of macrophages in vitro.
We showed that acute cold stress decreases phagocytosis of apoptotic cells at the inflammatory site by lipopolysaccharide-activated macrophages but did not affect resting macrophages. The inhibitory effect on phagocytosis is accompanied by a reduced level of TGF-beta and higher IL-10 secretion. After stress, plasma concentrations of corticosterone increased 6-fold, epinephrine 2-fold and norepinephrine 1.7-fold compared to control mice. In vitro experiments showed that the decrease in phagocytosis after stress could be attributed, at least in part, to the effects of corticosterone; epinephrine and norepinephrine had no effect.
The current study shows that acute cold stress decreases phagocytosis of apoptotic cells from an inflammatory environment by macrophages, and this inhibition is mediated by the intracellular glucocorticoid receptor.
压力可以改变免疫反应的许多方面，许多研究已经探讨了压力对炎症过程的影响，但对于其对组织稳态中炎症消退的影响知之甚少，这包括巨噬细胞以非炎症方式清除凋亡细胞。在本研究中，我们研究了急性冷应激对巨噬细胞吞噬凋亡细胞的影响。
将小鼠暴露于急性冷应激（4°C 4 小时），评估腹腔巨噬细胞吞噬凋亡胸腺细胞和分泌抗炎细胞因子的能力。检测血浆皮质酮和儿茶酚胺水平，以评估其对体外巨噬细胞吞噬能力的影响。
我们发现，急性冷应激降低了脂多糖激活的巨噬细胞在炎症部位吞噬凋亡细胞的能力，但对静止巨噬细胞没有影响。吞噬作用的抑制伴随着 TGF-β水平降低和 IL-10 分泌增加。应激后，与对照小鼠相比，血浆皮质酮浓度增加了 6 倍，肾上腺素增加了 2 倍，去甲肾上腺素增加了 1.7 倍。体外实验表明，应激后吞噬作用的降低至少部分归因于皮质酮的作用；肾上腺素和去甲肾上腺素没有影响。
本研究表明，急性冷应激可降低巨噬细胞从炎症环境中吞噬凋亡细胞的能力，这种抑制是通过细胞内糖皮质激素受体介导的。
