Smith W, Feldmann M, Londei M
The TVW Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia.
Eur J Immunol. 1998 Aug;28(8):2498-507. doi: 10.1002/(SICI)1521-4141(199808)28:08<2498::AID-IMMU2498>3.0.CO;2-Q.
IL-12 is important for Th1 differentiation. Myeloid-derived antigen-presenting cells (APC) such as monocytes, macrophages (Mphi) and dendritic cells (DC) are believed to be major sources of IL-12 in vivo. We have compared IL-12 production of fresh monocytes with Mphi differentiated in vitro using macrophage colony-stimulating factor (M-CSF) or human plasma, and in vitro generated dendritic cells, since these differentiated cell types represent APC at sites of antigen challenge. Macrophages stimulated with lipopolysaccharide (LPS) or heat-killed Listeria monocytogenes in the presence or absence of IFN-gamma produced minimal IL-12 p70 by comparison with DC or monocytes, despite comparable production of TNF-alpha. M-CSF-induced Mphi produced low levels of IL-10 constitutively and high levels after stimulation with LPS, but neutralization of IL-10 did not augment Mphi IL-12 production. Exposure of Mphi to TNF-alpha, granulocyte-macrophage CSF or IFN-gamma did not substantially up-regulate IL-12. Therefore M-CSF induces a differentiated Mphi phenotype in which IL-12 production is down-regulated, perhaps irreversibly. This may be the default pathway for monocyte-Mphi development in the absence of inflammation.
白细胞介素-12（IL-12）对Th1细胞分化很重要。髓系来源的抗原呈递细胞（APC），如单核细胞、巨噬细胞（Mphi）和树突状细胞（DC），被认为是体内IL-12的主要来源。我们比较了新鲜单核细胞、使用巨噬细胞集落刺激因子（M-CSF）或人血浆在体外分化的Mphi以及体外生成的树突状细胞产生IL-12的情况，因为这些分化的细胞类型代表了抗原攻击部位的APC。与DC或单核细胞相比，在有或没有干扰素-γ（IFN-γ）存在的情况下，用脂多糖（LPS）或热灭活的单核细胞增生李斯特菌刺激的巨噬细胞产生的IL-12 p70极少，尽管肿瘤坏死因子-α（TNF-α）的产生相当。M-CSF诱导的Mphi组成性地产生低水平的IL-10，在用LPS刺激后产生高水平的IL-10，但中和IL-10并没有增加Mphi的IL-12产生。将Mphi暴露于TNF-α、粒细胞-巨噬细胞集落刺激因子或IFN-γ并没有显著上调IL-12。因此，M-CSF诱导了一种分化的Mphi表型，其中IL-12的产生被下调，可能是不可逆的。这可能是在没有炎症的情况下单核细胞向Mphi发育的默认途径。
