McFadden R G, Bishop M A, Caveney A N, Fraher L J
Lawson Research Institute of St. Joseph's Health Centre, London, Ontario, Canada.
Thorax. 1995 Mar;50(3):265-9. doi: 10.1136/thx.50.3.265.
There is growing evidence to suggest the importance of the lymphocyte in the pathogenesis of asthma, particularly in the late phase reactions and ongoing bronchial hyperreactivity. Platelet activating factor (PAF) has also been identified as a potentially important mediator in asthma.
The migration of human peripheral blood lymphocytes obtained from normal volunteers in response to PAF and the effect of PAF antagonists was studied in a well standardised in vitro assay using nitrocellulose micropore filters in a microchemotaxis chamber.
PAF is a potent stimulus to in vitro human lymphocyte migration; at an optimal concentration of 1 nM it augmented lymphocyte chemokinesis to 310% (SE 33%) of control values. The response to PAF appears to be specific since lyso-PAF and other related membrane phospholipids had no effect. PAF-induced migration could be abrogated by specific PAF receptor antagonists such as WEB 2086 (100 nM), and was partially blocked by the cyclooxygenase inhibitor flurbiprofen at a concentration of 1 microM.
PAF stimulates the in vitro migration of human lymphocytes through a specific PAF receptor. Part of the response may be due to the generation of cyclooxygenase products. PAF may play a part in the recruitment of lymphocytes to asthmatic airways.
越来越多的证据表明淋巴细胞在哮喘发病机制中具有重要作用,尤其是在迟发相反应和持续性支气管高反应性方面。血小板活化因子(PAF)也被确定为哮喘中一种潜在的重要介质。
在微趋化室中使用硝酸纤维素微孔滤膜,通过一项标准化的体外试验,研究了从正常志愿者获取的人外周血淋巴细胞对PAF的迁移反应以及PAF拮抗剂的作用。
PAF是体外人淋巴细胞迁移的有效刺激物;在1 nM的最佳浓度下,它将淋巴细胞趋化运动增强至对照值的310%(标准误33%)。由于溶血PAF和其他相关膜磷脂没有作用,对PAF的反应似乎具有特异性。PAF诱导的迁移可被特异性PAF受体拮抗剂如WEB 2086(100 nM)消除,并且在1 microM的浓度下被环氧化酶抑制剂氟比洛芬部分阻断。
PAF通过特异性PAF受体刺激人淋巴细胞的体外迁移。部分反应可能归因于环氧化酶产物的生成。PAF可能在淋巴细胞向哮喘气道的募集过程中发挥作用。