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Induction of functionally active platelet-activating factor receptors in rat alveolar macrophages.

K. Pendino,C. Gardner,J. Laskin,D. Laskin

Published 1993 in Journal of Biological Chemistry

ABSTRACT

Freshly isolated alveolar macrophages from control rats express low numbers of platelet-activating factor (PAF) receptors (4.6 x 10(3) binding sites/cell, Kd = 1.3 nM). These receptors appeared to be functionally inert in that PAF failed to induce intracellular calcium mobilization in the cells. Following brief exposure of rats to ozone (2 ppm, 3 h), a pulmonary irritant and inflammatory agent that is rapidly converted to molecular oxygen, expression of PAF receptors was markedly up-regulated on lung phagocytes (13.1 x 10(3) binding sites/cell), with no significant effect on receptor affinity (Kd = 2.0 nM). In these cells, PAF, but not lyso-PAF, an inactive analog, caused a rapid and transient rise in intracellular calcium demonstrating that the PAF receptors were functionally active. The calcium response to PAF, which was largely due to mobilization of calcium from intracellular stores, was found to be dose-dependent in the nanomolar concentration range and inhibitable by the PAF receptor antagonist triazolam. The results of these studies may be important in elucidating mechanisms of lung inflammation induced by this model irritant.

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