Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma
Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma
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DOI：
10.4049/jimmunol.176.3.1860
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Tunon-de-Lara, JM
中科院分区：
文献类型：
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作者：
El-Shazly, A;Berger, P;Tunon-de-Lara, JM
人气道平滑肌细胞 (HASMC) 分泌 fractalkine (FKN)，这是一种趋化因子，哮喘患者的浓度会增加。 HASMC 还诱导肥大细胞趋化性，作为哮喘炎症的一个组成部分。因此，我们评估了平滑肌来源的 FKN 在肥大细胞迁移中的作用。我们评估了重组 FKN 诱导人肥大细胞趋化性的能力。这种效应涉及涉及肌动蛋白重组和蛋白激酶 C-δ 的钙独立途径。我们发现 HASMC 组成型产生 FKN，其合成在促炎刺激下得到加强。在基础实验条件下，HASMC 产生的 FKN 不足以诱导肥大细胞趋化性。然而，用神经肽血管活性肠肽 (VIP) 预处理肥大细胞可增加 FKN 吸引肥大细胞的效力。由于我们在哮喘患者中观察到气道平滑肌 FKN 和 VIP 表达均增加，并且 VIP 染色与平滑肌层肥大细胞浸润呈正相关，因此我们得出结论，HASMC 衍生的 FKN 可能有助于哮喘中肥大细胞的募集。
Human airway smooth muscle cells (HASMC) secrete fractalkine (FKN), a chemokine the concentration of which is increased in asthmatic patients. HASMC also induce mast cell chemotaxis, as a component of asthma inflammation. We therefore evaluated the role of smooth muscle-derived FKN in mast cell migration. We assessed the capacity of recombinant FKN to induce human mast cell chemotaxis. This effect implicates a calcium-independent pathway involving actin reorganization and protein kinase C-delta. We found that HASMC constitutively produce FKN, the synthesis of which is reinforced upon proinflammatory stimulation. Under basal experimental conditions, FKN production by HASMC is not sufficient to induce mast cell chemotaxis. However, pretreatment of mast cells with the neuropeptide vasoactive intestinal peptide (VIP) increases FKN potency to attract mast cells. Since we observed, in asthmatic patients, an increase in both FKN and VIP expression by airway smooth muscle and a positive correlation between VIP staining and mast cell infiltration of the smooth muscle layer, we conclude that HASMC-derived FKN may contribute to mast cell recruitment in asthma.