Activation of the phagocytic system increases intimal proliferation in hypercholesterolemic rabbits

The effect of in vivo stimulation of the phagocytic system (neutrophils, monocytes and hepatic Kupffer-cells) by inducing phagocytosis of intravenously administered latex particles on lipid peroxidation and aortic intimal proliferation was tested in cholesterol-fed rabbits. Three weeks after starting the diet, aortic intimal proliferation was measured by the intimal to medial ratios and by the incorporation of [3H]thymidine, infused into the circulation for the preceding 14 days. Intimal to medial ratios were increased (0.473 +/- 0.023 vs. 0.282 +/- 0.011, P < 0.01) and aortic [3H]thymidine contents were higher (66.8 +/- 3.5 vs. 27.8 +/- 49 counts/min per mg, P = 0.0001) in latex bead-treated than in control animals. Injection of beads transiently increased plasma lipid peroxide levels. At the end of the 3 week experiment, plasma lipid peroxide levels were still elevated and lipid peroxide contents of the aortic walls were higher in the latex-treated rabbits (82.8 +/- 5.8 vs. 46.4 +/- 4.9 nmol/mg cholesterol, latex-treated vs. controls, P = 0.004). These data suggest a significant acceleration of atherogenesis by the stimulated phagocytic system, the mechanism of which may involve lipid peroxidation.