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首页> 外文期刊>Infection and immunity >Differential Responses of Human Mononuclear Phagocytes to Mycobacterial Lipoarabinomannans: Role of CD14 and the Mannose Receptor
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Differential Responses of Human Mononuclear Phagocytes to Mycobacterial Lipoarabinomannans: Role of CD14 and the Mannose Receptor

机译:人类单核吞噬细胞对分枝杆菌脂肪寡糖甘露聚糖的不同反应:CD14和甘露糖受体的作用。

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CD14 is a signaling receptor for both gram-negative bacterial lipopolysaccharide (LPS) and mycobacterial lipoarabinomannan (LAM) that lacks terminal mannosyl units (AraLAM). In contrast, terminally mannosylated LAM (ManLAM) binds the macrophage mannose receptor (MMRc), although the ability of the MMRc to serve as a signaling receptor has not been previously reported. We compared the abilities of AraLAM and ManLAM to induce distinct responses in two monocytic cell populations, freshly isolated human peripheral blood monocytes (PBM) and monocyte-derived macrophages (MDM). The responses examined were chemotaxis and transient changes in free cytosolic calcium ([Ca2+]in). We found that AraLAM but not ManLAM was chemotactic for both PBM and MDM. Migration of these cells in vitro to AraLAM was specifically blocked by an anti-CD14 monoclonal antibody, suggesting that CD14 mediates the chemotactic response to AraLAM. Subsequently, we found that AraLAM induced a transient rise in [Ca2+]in levels within a subpopulation of PBM but not MDM. This response was blocked by anti-CD14 antibodies. In contrast, ManLAM induced a transient rise in [Ca2+]in levels within a subpopulation of MDM but not PBM. This response was blocked by either anti-CD14 or anti-MMRc antibodies. These data suggest that the MMRc can serve as a signaling receptor and that coligation of both CD14 and the MMRc is required to elicit a specific response. Thus, one response to LAM (chemotaxis) can be elicited solely by engaging CD14, whereas a different response (changes in [Ca2+]in levels) depends on both the differentiation state of the cells and concomitant engagement of CD14 and the MMRc.
机译:CD14是革兰氏阴性细菌脂多糖(LPS)和缺乏末端甘露糖基单元(AraLAM)的分枝杆菌脂阿拉伯甘露聚糖(LAM)的信号受体。相反,末端甘露糖基化的LAM(ManLAM)结合巨噬细胞甘露糖受体(MMRc),尽管以前尚未报道过MMRc充当信号受体的能力。我们比较了AraLAM和ManLAM在两个单核细胞群体,新鲜分离的人外周血单核细胞(PBM)和单核细胞衍生的巨噬细胞(MDM)中诱导不同反应的能力。检查的反应是趋化性和游离胞质钙([Ca 2 + ] in 中)的瞬时变化。我们发现AraLAM但不是ManLAM对PBM和MDM都是趋化性的。这些细胞在体外向AraLAM的迁移被抗CD14单克隆抗体特异性阻断,表明CD14介导了对AraLAM的趋化反应。随后,我们发现AraLAM在PBM的亚群中引起了[Ca 2 + ] in 中的瞬时升高,但没有引起MDM。该反应被抗CD14抗体阻断。相比之下,ManLAM导致MDM子群体中的[Ca 2 + ] in 中的瞬时升高,而PBM却没有。该反应被抗CD14或抗MMRc抗体阻断。这些数据表明,MMRc可以作为信号受体,并且需要CD14和MMRc的凝结才能引起特异性反应。因此,仅通过使CD14参与即可引起对LAM(趋化性)的一种反应,而不同的反应([Ca 2 + ] 含量的变化)取决于两者。细胞的分化状态以及CD14和MMRc的伴随结合。

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