Increased adhesiveness of isolated monocytes to endothelium is prevented by vitamin C intake in smokers.

To explore pathophysiological mechanisms of cigarette smoking involved in atherogenesis, we compared adhesiveness of isolated blood monocytes with endothelium and plasma levels of the aqueous phase antioxidant vitamin C in nonsmokers and smokers before and after supplementation, using a novel monocyte adhesion assay with fixed human endothelial cells. Monocyte adhesion to unstimulated human umbilical vein endothelial cells ranged from 0.17% to 0.51% in the nonsmoker group (0.37+/-0.09%, mean +/-SD, n=13). In smokers with a 1 to 2 packs per day consumption, monocyte adhesion was increased to 0.71+/-0.17% (mean +/-SD, n=10, P<.001), ranging from 0.46% to 0.99%. Increased adhesiveness was mediated by the integrin CD11b/CD18, as shown by inhibition with a monoclonal antibody to CD11b but not associated with altered CD11b surface expression. Plasma vitamin C levels were reduced in smokers (48.2+/-14.1 micromol/L) versus nonsmokers (67.7+/-17.6 micromol/L; P<.025), while no significant differences were found in retinol, vitamin E, or beta-carotene levels. This confirms that the radical scavenger vitamin C reacts sensitively to oxidative stress induced by cigarette smoke in human plasma. Consistently, dietary supplementation with vitamin C (2 g per day) for 10 days raised plasma levels to 82.6+/-11.0 micromol/L (n=10, P<.001) in smokers and decreased monocyte adhesion to values found in nonsmokers (0.38+/-0.18%, P<.001). In contrast, vitamin C intake did not affect monocyte adhesiveness in nonsmokers (0.37+/-0.14%, n=6) despite increasing plasma levels to 82.9+/-11.8 micromol/L. Our data show that cigarette smoking increases CD11b-dependent monocyte adhesiveness in humans. Restoring reduced plasma vitamin C concentrations in smokers by oral supplementation decreased monocyte adhesion to values found in nonsmokers.