ELEVATED INTRACELLULAR CYCLIC-AMP INHIBITS CHEMOTAXIS IN HUMAN EOSINOPHILS

Elevated intracellular cyclic AMP is associated with the inhibition of many inflammatory cellular responses. In this study, we examined the effect of cyclic AMP on eosinophil chemotaxis. Eosinophils were isolat ed from healthy human volunteers using an immunomagnetic method. Eosin ophils were treated with agents that elevate intracellular cyclic AMP and evaluated for chemotactic responses to platelet-activating factor (PAF; 10(-6) M) and to complement factor 5a (C5a; 10(-8) M) in microch emotaxis chambers. Forskolin, prostaglandin E(1) (PGE(1)), and a phosp hodiesterase (PDE) IV-selective inhibitor inhibited eosinophil chemota ctic responses. The mean per cent inhibition of eosinophil chemotaxis in response to PAF by forskolin, PGE(1), and the PDE IV-selective inhi bitor (10(-5) M) was 16.8 +/- 5.3, 26.6 +/- 9.5, and 35.1 +/- 6.1%, re spectively (n = 5). The corresponding values for C5a were 17.5 +/- 7.9 , 20.8 +/- 10.7, and 39.5 +/- 5.0%. An exogenous cyclic AMP analogue ( dibutyryl cyclic AMP, 10(-3) M) also inhibited eosinophil chemotaxis b y 69.4 +/- 12.8 and 66.9 +/- 11.6% in response to PAF and C5a, respect ively (n = 5). We conclude that elevated intracellular cyclic AMP inhi bits eosinophil chemotaxis.