Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO
Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO
复制标题
DOI：
10.4049/jimmunol.175.12.8032
复制
发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Kobzik, L
中科院分区：
文献类型：
--
作者：
Józefowski, S;Arredouani, M;Kobzik, L
巨噬细胞A类清除受体，胶原结构巨噬细胞受体（MARCO）和I/II型A类清除受体（SR-AI/II），在宿主防御中具有相同的结构特征和作用，但对其调控和信号传导特性知之甚少。用固定的单抗将MARCO结扎在巯基乙酸酯诱导的小鼠腹腔巨噬细胞（PEMs）上，共刺激IL-12的产生。与之前报道的SR-AI/II的抑制作用相反。来自marco缺陷小鼠的PEMs在LPS和ifn - γ刺激下显示出2.7倍的IL-12产生降低，并且在单独LPS刺激下缺乏显著的IL-12产生。相反，SR-AI/ ii缺陷的PEMs在LPS或LPS和ifn - γ作用下产生的IL-12分别是野生型PEMs的2.4倍和1.8倍。SR-A和MARCO的表达调控也存在相应差异。Th1佐剂（LPS，含有CpG基元的寡脱氧核苷酸（CpG-ODN）， IL-12和GMCSF）增加，而th2极化因子（IL-4， M-CSF和非CpG ODN）降低了J774巨噬细胞样细胞上MARCO的表达。SR-A的表达与MARCO相反或不受影响。而在cpg - odn预处理的J774细胞中，MARCO参与opsonin-independent吞噬，而在il -4预处理的J774细胞中则不参与；抗sr - a抗体在未处理和il -4预处理的J774细胞中抑制颗粒摄取，但在cpg - odn预处理的J774细胞中无抑制作用。SR-A和MARCO受到不同的调控，对巨噬细胞IL-12的产生有不同的正、负作用。这些差异可能有助于持续免疫反应的持续Th1或Th2极化。
The macrophage class A scavenger receptors, macrophage receptor with a collagenous structure (MARCO) and type I/II class A scavenger receptor (SR-AI/II), share structural features and roles in host defense, but little is known about their regulation and signaling properties. Ligation of MARCO on mouse thioglycollate-elicited peritoneal macrophages (PEMs) with immobilized mAb costimulated IL-12 production., in contrast to previously reported inhibition by SR-AI/II. PEMs from MARCO-deficient mice exhibited 2.7 times lower IL-12 production in responses to stimulation with LPS and IFN-gamma and lack of significant IL-12 production on stimulation with LPS alone. Conversely, SR-AI/II-deficient PEMs produced 2.4 and 1.8 times more IL-12 than wildtype PEMs in response to LPS or LPS and IFN-gamma, respectively. Corresponding differences in regulation of SR-A and MARCO expression were also observed. Th1 adjuvants (LPS, a CpG motif-containing oligodeoxynucleotide (CpG-ODN), IL-12, and GMCSF) increased, whereas Th2-polarizing factors (IL-4, M-CSF, and non-CpG ODN) decreased expression of MARCO on J774 macrophage-like cells. Expression of SR-A was regulated in the opposite manner to MARCO or not affected. Whereas MARCO was involved in opsonin-independent phagocytosis in CpG-ODN-pretreated but not in IL-4-pretreated J774 cells, anti-SR-A Abs inhibited particle uptake in untreated and IL-4-pretreated but not in CpG-ODN-pretreated cells. SR-A and MARCO are regulated differently and mediate distinct negative and positive effects on IL-12 production in macrophages. These differences may contribute to sustained Th1 or Th2 polarization of ongoing immune responses.