Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus
Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus
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DOI：
10.1152/ajpgi.00453.2007
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发表时间：
2008-03-01
影响因子：
4.5
通讯作者：
Collins, Stephen
中科院分区：
文献类型：
--
作者：
Ghia, Jean-Eric;Galeazzi, Francesca;Collins, Stephen
尽管巨噬细胞被认为是决定肠道急性炎症反应严重程度的关键因素，但最近的证据表明，巨噬细胞也可能发挥抗炎作用。在这项研究中，我们研究了巨噬细胞亚群在两种结肠炎模型中的作用。研究了巨噬细胞集落刺激因子（M-CSF）缺乏的骨质疏松小鼠（op/op）和表达M-CSF的杂合子（+/?）小鼠在二硝基苯磺酸（DNBS）或葡聚糖硫酸钠（DSS）诱导结肠炎后的反应。与+/?相比，DNBS诱导m - csf缺乏的op/op小鼠出现严重结肠炎。老鼠。这与死亡率增加和更严重的宏观和微观损伤有关。DNBS结肠炎op/op小鼠结肠组织髓过氧化物酶（MPO）活性以及tnf - α、IL-1 β和IL-6浓度升高，IL-10浓度降低。在结肠炎诱导前接受人重组M-CSF的op/op小鼠，炎症的严重程度和死亡率降低。相比之下，op/op小鼠对DSS诱导的结肠炎的易感性较低。与+/?相比，op/op小鼠的宏观损伤、微观损伤、MPO活性以及组织中tnf - α、IL-1 β和IL-6的浓度均较低。DSS结肠炎小鼠，IL-10未见变化。巨噬细胞炎症蛋白-1 α浓度在op/op组升高，而在+/？DNBS诱导小鼠结肠炎，DSS则不存在。这些结果表明，依赖m - csf的巨噬细胞可能在急性实验性结肠炎中发挥促炎或抗炎作用，这取决于用于诱导结肠炎的刺激。
Although macrophages are considered a critical factor in determining the severity of acute inflammatory responses in the gut, recent evidence has indicated that macrophages may also play a counterinflammatory role. In this study, we examined the role of a macrophage subset in two models of colitis. Macrophage colony-stimulating factor (M-CSF)-deficient osteopetrotic mice (op/op) and M-CSF-expressing heterozygote (+/?) micewere studied following the induction of colitis by either dinitrobenzene sulfonic acid ( DNBS) or dextran sulfate sodium (DSS). DNBS induced a severe colitis in M-CSF-deficient op/op mice compared with +/? mice. This was associated with increased mortality and more severe macroscopic and microscopic injury. Colonic tissue myeloperoxidase (MPO) activity as well as concentrations of TNF-alpha, IL-1 beta, and IL-6 were higher and IL-10 lower in op/op mice with DNBS colitis. The severity of inflammation and mortality was attenuated in op/op mice that had received human recombinant M-CSF prior to the induction of colitis. In contrast, op/op mice appeared less vulnerable to colitis induced by DSS. Macroscopic damage, microscopic injury, MPO activity, and tissue concentrations of TNF-alpha, IL-1 beta, and IL-6 were all lower in op/op mice compared with +/? mice with DSS colitis, and no changes were seen in IL-10. Macrophage inflammatory protein-1 alpha concentrations were increased in op/op but not +/? mice following colitis induced by DNBS but not DSS. These results indicate that M-CSF-dependent macrophages may play either a pro-or counterinflammatory role in acute experimental colitis, depending on the stimulus used to induce colitis.