Interaction between activated chemokine receptor 1 and FcεRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells
Interaction between activated chemokine receptor 1 and FcεRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells
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DOI：
10.1093/intimm/dxp118
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发表时间：
2010-02-01
影响因子：
4.4
通讯作者：
Ono, Santa J.
中科院分区：
文献类型：
--
作者：
Fifadara, Nimita H.;Beer, Freddy;Ono, Santa J.
趋化因子在免疫中发挥重要的调节作用，但其对肥大细胞功能的贡献仍然知之甚少。我们研究了Fc γ-趋化因子受体（CCR）1共刺激对骨髓源性肥大细胞受体定位和细胞形态的影响。而Fc β RI和CCR 1共定位于未致敏细胞的质膜上，用IgE致敏促进CCR 1分子的内化。与抗原和巨噬细胞炎性蛋白-1 α共同刺激Fc β RI和CCR 1比单独刺激Fc β RI在引起前缘形成、扁平形态、膜皱褶和神经节苷脂（GM 1（+））脂质介质释放方面更有效。共刺激导致鬼笔环肽阳性细胞丝样细胞延伸，也称为隧道纳米管，其起源于钙积累点。这是首次报道肥大细胞形成细胞丝。为了确定脂筏对肥大细胞功能的重要性，将细胞胆固醇耗尽。胆固醇耗竭增强了静息、致敏和共刺激细胞的脱粒，但在Fc β RI交联细胞中没有，并抑制了丝状肌动蛋白（+）细胞丝素的形成，但不抑制GM 1（+）细胞丝素的形成。用latrunculin A隔离球状肌动蛋白的处理废除了细胞丝的形成。在过敏和炎症反应过程中，cytonemes可能参与细胞间通讯，它们在共同刺激的肥大细胞中的存在表明CCR在免疫病理学中的新作用。
Chemokines play important regulatory roles in immunity, but their contributions to mast cell function remain poorly understood. We examined the effects of Fc epsilon RI-chemokine receptor (CCR) 1 co-stimulation on receptor localization and cellular morphology of bone marrow-derived mast cells. Whereas Fc epsilon RI and CCR1 co-localized at the plasma membrane in unsensitized cells, sensitization with IgE promoted internalization of CCR1 molecules. Co-stimulation of Fc epsilon RI and CCR1 with antigen and macrophage inflammatory protein-1 alpha was more effective than Fc epsilon RI stimulation alone in causing leading edge formation, flattened morphology, membrane ruffles and ganglioside (GM1(+)) lipid mediator release. Co-stimulation resulted in phalloidin-positive cytoneme-like cellular extensions, also known as tunneling nanotubes, which originated at points of calcium accumulation. This is the first report of cytoneme formation by mast cells. To determine the importance of lipid rafts for mast cell function, the cells were cholesterol depleted. Cholesterol depletion enhanced degranulation in resting, sensitized and co-stimulated cells, but not in Fc epsilon RI-cross-linked cells, and inhibited formation of filamentous actin(+) cytonemes but not GM1(+) cytonemes. Treatment with latrunculin A to sequester globular-actin abolished cytoneme formation. The cytonemes may participate in intercellular communication during allergic and inflammatory responses, and their presence in the co-stimulated mast cells suggests new roles for CCRs in immunopathology.