Inhibition of human polymorphonuclear leukocyte chemotaxis by oxygenated sterol compounds

When preincubated with certain oxygenated sterol compounds in lipoprotein-depleted serum [20% (vol/vol)], human polymorphonuclear leukocytes show inhibition of chemotaxis toward the synthetic dipeptide N-formylmethionyl-phenylalanine without alteration of random movement or loss of cell viability. These effects can occur at sterol concentrations as low as 6.25 μM and after as little as 5 min of preincubation, but they are increased at higher concentrations and longer preincubation times. The inhibition can be almost completely reversed by preincubation in lipoprotein-replete serum [human AB serum, 20% (vol/vol)] and may be partially corrected by addition of free cholesterol (0.125 mM) to the medium. These effects are unlikely to be due to inhibition of cellular sterol synthesis, competition for chemotaxin membrane binding sites, or deactivation of the leukocytes but they may be a consequence of insertion of the sterol molecule into the leukocyte plasma membranes.