Clearance of apoptotic cells by macrophages induces regulatory phenotype and involves stimulation of CD36 and platelet-activating factor receptor.
Clearance of apoptotic cells by macrophages induces regulatory phenotype and involves stimulation of CD36 and platelet-activating factor receptor.
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DOI：
10.1155/2013/950273
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发表时间：
2013
影响因子：
4.6
通讯作者：
Jancar S
中科院分区：
文献类型：
--
作者：
Ferracini M;Rios FJ;Pecenin M;Jancar S
凋亡细胞的吞噬作用（吞噬细胞）诱导巨噬细胞向调节表型（IL-10高/IL-12 p40低）分化。CD 36参与凋亡细胞（AC）的识别，我们已经证明血小板活化因子受体（PAFR）也参与其中。在这里，我们研究了PAFR和CD 36对巨噬细胞增多和建立调节性巨噬细胞表型的贡献。小鼠骨髓源性巨噬细胞与凋亡胸腺细胞共培养，测定吞噬指数。用拮抗剂阻断PAFR或用特异性抗体阻断CD 36可抑制AC的吞噬作用（约70-80%）。使用免疫沉淀和共聚焦显微镜，我们发现，AC吞噬增加了CD 36和PAFR在巨噬细胞质膜的共定位; PAFR和CD 36与flotillin-1（一种组成性脂筏蛋白）共免疫沉淀，甲基-β-环糊精破坏这些膜微区降低了AC的吞噬作用。胞饮作用诱导的细胞因子的生产模式，IL-10高/IL-12 p40低，即一个监管表型的特征。LPS增强了巨噬细胞诱导的IL-10的产生，这是通过阻断PAFR或CD 36来防止的。可以得出结论，凋亡细胞的吞噬作用涉及CD 36和PAFR，可能在脂筏中，这是最佳的吞噬作用和巨噬细胞调节表型的建立所必需的。
Phagocytosis of apoptotic cells (efferocytosis) induces macrophage differentiation towards a regulatory phenotype (IL-10high/IL-12p40low). CD36 is involved in the recognition of apoptotic cells (AC), and we have shown that the platelet-activating factor receptor (PAFR) is also involved. Here, we investigated the contribution of PAFR and CD36 to efferocytosis and to the establishment of a regulatory macrophage phenotype. Mice bone marrow-derived macrophages were cocultured with apoptotic thymocytes, and the phagocytic index was determined. Blockage of PAFR with antagonists or CD36 with specific antibodies inhibited the phagocytosis of AC (~70–80%). Using immunoprecipitation and confocal microscopy, we showed that efferocytosis increased the CD36 and PAFR colocalisation in the macrophage plasma membrane; PAFR and CD36 coimmunoprecipitated with flotillin-1, a constitutive lipid raft protein, and disruption of these membrane microdomains by methyl-β-cyclodextrin reduced AC phagocytosis. Efferocytosis induced a pattern of cytokine production, IL-10high/IL-12p40low, that is, characteristic of a regulatory phenotype. LPS potentiated the efferocytosis-induced production of IL-10, and this was prevented by blocking PAFR or CD36. It can be concluded that phagocytosis of apoptotic cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype.
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