INDUCTION OF FUNCTIONALLY ACTIVE PLATELET-ACTIVATING-FACTOR RECEPTORSIN RAT ALVEOLAR MACROPHAGES

Freshly isolated alveolar macrophages from control rats express low nu mbers of platelet-activating factor (PAF) receptors (4.6 x 10(3) bindi ng sites/cell, K(d) = 1.3 nM). These receptors appeared to be function ally inert in that PAF failed to induce intracellular calcium mobiliza tion in the cells. Following brief exposure of rats to ozone (2 ppm, 3 h), a pulmonary irritant and inflammatory agent that is rapidly conve rted to molecular oxygen, expression of PAF receptors was markedly up- regulated on lung phagocytes (13.1 x 10(3) binding sites/cell), with n o significant effect on receptor affinity (K(d) = 2.0 nM). In these ce lls, PAF, but not lyso-PAF, an inactive analog, caused a rapid and tra nsient rise in intracellular calcium demonstrating that the PAF recept ors were functionally active. The calcium response to PAF, which was l argely due to mobilization of calcium from intracellular stores, was f ound to be dose-dependent in the nanomolar concentration range and inh ibitable by the PAF receptor antagonist triazolam. The results of thes e studies may be important in elucidating mechanisms of lung inflammat ion induced by this model irritant.