LONG-TIME INCUBATION OF MONOCYTIC U-937 CELLS WITH LDL INCREASES SPECIFIC PAF-ACETHER BINDING AND THE CELLULAR ACETYLHYDROLASE ACTIVITY

Besides the well established role of low density lipoproteins (LDL), the phospholipid PAF-acether (paf) seems to be involved in atherogenesis. The effect of LDL (10-mu-g/ml for 24 h, n = 3) on paf binding characteristics of monocyte/macrophage-like U 937 cells was investigated using the radioligand [H-3]paf, unlabeled paf and the paf receptor antagonist WEB 2086. The specific [H-3]paf binding significantly increased at 1.4 nM (P < 0.02) and 2.8 nM (P < 0.01) added [H-3]paf with an increased number of paf binding sites in the Scatchard plot analysis of the data. Specific paf binding was functionally active since paf mediated a cellular [Ca2+]i rise. The protein kinase C (PKC) activator PMA (1 nM, 37-degrees-C) expressed specific [H-3]paf binding already after a 15-min incubation period, indicating a PKC activation as the decisive step of paf receptor expression. LDL also stimulated the paf degrading cellular acetylhydrolase significantly by increasing both K(m) (9.4 +/- 1.9 vs. 2.0 +/- 0.5-mu-M, P < 0.02) and nu-max (0.5 +/- 0.2 vs. 0.2 +/- 0.0 nmol/min per mg cell protein, P < 0.02). The data demonstrate that LDL increases the number of paf receptors on monocyte/macrophage-like U 937 cells and interferes with the dynamics and/or synthesis of the cellular acetyl hydrolase. These effects could be of importance in the pathogenesis of atherosclerosis.