Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation

Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation
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DOI:
10.1111/j.1365-2005.02932.x
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发表时间:
2005-12-01
影响因子:
4.6
通讯作者:
Yachie, A
Yachie, A
中科院分区:
医学3区
文献类型:
--
作者:
Mizuno, K;Toma, T;Yachie, A

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单核细胞在外周血中由两个不同的亚群组成,这取决于它们的表面抗原表达、细胞因子产生的分布和在体内发挥的功能作用。我们试图描述CD16(高)Ccr(2-)亚群的循环单核细胞所扮演的独特功能。它们在体外刺激时产生显著水平的白介素6和肿瘤坏死因子α,但产生非常低水平的白介素10。细胞分选后刺激纯化的单核细胞亚群,确认细胞因子产生的特征。值得注意的是,新鲜分离的CD16(高)Ccr(2-)单核细胞亚群产生显著水平的血红素氧合酶(HO)-1,而主要的CD16(低)Ccr(2+)亚群产生很少。这些结果与普遍接受的观念相反,即CD16(高)CCR(2-)单核细胞亚群在体内起主要的促炎作用。CD16(高)Ccr(2-)亚群在川崎病和流感病毒感染中升高。与此相一致的是,在这些疾病中,单个核细胞HO-1mRNA的表达显著增加。这些结果表明CD16(高)Ccr(2-)亚群与CD16(低)Ccr(2+)单核细胞具有不同的谱系。更重要的是,它们可能代表了一个单核细胞亚群,具有独特的功能,通过在体内稳定地产生HO-1来调节炎症。
Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR(2-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR(2-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR(2+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR(2-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR(2-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR(2-) subpopulations are of a distinct lineage from CD16(low)CCR(2+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.