EFFECT OF PLATELET-ACTIVATING-FACTOR (PAF) ON THE MIGRATION OF HUMAN-LYMPHOCYTES

Background - There is growing evidence to suggest the importance of th e lymphocyte in the pathogenesis of asthma, particularly in late phase reactions and ongoing bronchial hyperreactivity. Platelet activating factor (PAF) has also been identified as a potentially important media tor in asthma. Methods - The migration of human peripheral blood lymph ocytes obtained from normal volunteers in response to PAF and the effe ct of PAF antagonists was studied in a well standardised in vitro assa y using nitrocellulose micropore filters in a microchemotaxis chamber. Results - PAF is a potent stimulus to in vitro human lymphocyte migra tion; at an optimal concentration of 1 nM it augmented lymphocyte chem okinesis to 310% (SE 33%) of control values. The response to PAF appea rs to be specific since lyso-PAF and other related membrane phospholip ids had no effect. PAF-induced migration could be abrogated by specifi c PAF receptor antagonists such as WEB 2086 (100 nM), and was partiall y blocked by the cyclooxygenase inhibitor flurbiprofen at a concentrat ion of 1 mu M. Conclusions - PAF stimulates the in vitro migration of human lymphocytes through a specific PAF receptor. Part of the respons e may be due to the generation of cyclooxygenase products. PAF may pla y a part in the recruitment of lymphocytes to asthmatic airways.