Regulation of interleukin-12 by complement receptor 3 signaling
Regulation of interleukin-12 by complement receptor 3 signaling
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DOI：
10.1084/jem.185.11.1987
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发表时间：
1997-06-02
影响因子：
15.3
通讯作者：
Kelsall, BL
中科院分区：
文献类型：
--
作者：
Marth, T;Kelsall, BL
补体受体3型（CR 3，CD 11b/CD 18）作为许多内源性配体和感染性生物体的受体，并参与粘附和宿主防御功能。在这里，我们报告说，通过CR 3信号在调节白细胞介素-12（IL-12），细胞介导的免疫（CMI）的关键介质的生产中起着重要作用。我们证明了在暴露于CR 3抗体（抗CD 11b和抗CD 18）以及天然CR 3配体iC 3b和荚膜组织胞浆菌后，通过多种刺激，中枢人单核细胞体外IL-12分泌的剂量依赖性、特异性下调。CR 3抗体还抑制人外周血单核细胞（PBMC）培养物中干扰素-γ（IFN-γ）的产生。我们确定CR 3抗体可抑制IL-12产生的一种机制是通过抑制IFN-γ诱导的酪氨酸磷酸化。最后，在IL-12依赖性脓毒性休克的鼠模型中，我们提供了CR 3抗体的施用导致体内IL-12和IFN-γ抑制的证据。因此，我们的研究确定了CR 3在通过IL-12调节CMI功能中的新作用。
Complement receptor type 3 (CR3, CD11b/CD18) serves as a receptor for a number of endogenous ligands and infectious organisms, and is involved in adhesion and host defense functions. Here, we report that signaling via CR3 plays an important role in regulating production of interleukin-12 (IL-12), a key mediator of cell-mediated immunity (CMI). We demonstrate with a variety of stimuli a dose-dependent, specific downregulation of IL-12 secretion by hub man monocytes in vitro after exposure to antibodies to CR3 (anti-CD11b and anti-CD18), as well as to the natural CR3 ligands, iC3b, and Histoplasma capsulatum. CR3 antibodies also suppressed interferon-gamma (IFN-gamma) production in cultures of human peripheral blood mononuclear cells (PBMC). We determined that one mechanism by which CR3 antibodies may suppress IL-12 production is by the inhibition of IFN-gamma-induced tyrosine phosphorylation. Finally, in a murine model of IL-12-dependent septic shock, we provide evidence that administration of CR3 antibodies leads to suppression of IL-12 and IFN-gamma in vivo. Our studies thus define a novel role for CR3 in regulating CMI functions via IL-12.