ATP及其代谢产物对肥大细胞趋化及活化作用

目的:研究三磷酸腺苷(ATP)对人肥大细胞(HMC)-1细胞趋化性以及白细胞介素(白介素)13(IL-13)、肿瘤坏死因子α(TNF-α)分泌水平的影响。方法:通过Transwell系统检测ATP对HMC-1趋化活性的影响。通过流式细胞术检测ATP刺激后肥大细胞表面趋化因子受体3(CXCR3)、CXCR4的表达水平变化。原代培养OVA-致敏并激发所致哮喘模型小鼠的气道平滑肌细胞,并用ELISA法检测ATP刺激后,培养细胞上清中白介素4(IL-4),IL-13,TNF-α的分泌水平。结果:ATP增强HMC-1的趋化活性。而经ATP刺激后,气道平滑肌细胞表达趋化因子配体10(CXCL10)以及HMC-1细胞表面表达的CXCR3均上调(P<0.05)。ATP及其稳定类似物ATPγS也可以增加HMC-1细胞IL-13以及TNF-α的表达(P<0.01),而ATP代谢产物ADP、腺苷刺激后则无这些作用。结论:ATP及其稳定类似物ATPγS可以上调HMC-1的趋化性以及分泌炎症因子,从而参与哮喘炎症反应过程。

Effect of ATP and Its Metabolites on Chemotaxis and Activation of Human Mast Cell-1

Objective: To study the the effect of ATP and its metabolites on human mast cell(HMC)-1 chemotaxis and the secretion of IL-4,IL-13 and TNF-α.Methods: Mast cell chemotaxis towards ATP and its antalogues ATPγS,ADP,adenosine were investigated by Transwell system.The expression and secretion level of mouse CXCL10 and human IL-4,IL-13,TNF-alpha,etc,were measured by ELISA,meanwhile the expression of CXCR3 and CXCR4 of HMC-1 stimulated with ATP were examined by flow cytometry. Results: ATP induces the HMC-1 cell chemotaxis.Both CXCL10 expression on arterial smooth muscle cells(ASMCs) and CXCR3 expression on HMC-1 increased markedly after ATP stimulation(P < 0. 05).The expression of IL-4,IL-13,and TNF-α of HMC-1 also increased when stimulated with ATP and its stable analogue ATPγS(P < 0.01).Conclusion: ATP and its stable analogue ATPγS can up-regulate the chemotaixs and activation of HMC-1,therefore take part in the initial and development of asthma.