VITAMIN-C PREVENTS CIGARETTE SMOKE-INDUCED LEUKOCYTE AGGREGATION AND ADHESION TO ENDOTHELIUM IN-VIVO

A common feature of cigarette-smoke (CS)-associated diseases such as a therosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro- and macrovascular endothelium. A previous study, using a skinfold chamber model for intravital fluores cence microscopy in awake hamsters, has shown that exposure of hamster s to the smoke generated by one research cigarette elicits the adhesio n of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and s canning electron microscopy, we now demonstrate in the same animal mod el that (i) CS-induced leukocyte adhesion is not confined to the micro circulation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstr eam of aggregates between leukocytes and platelets; and (iii) CS-induc ed leukocyte adhesion to micro- and macrovascular endothelium and leuk ocyte-platelet aggregate formation are almost entirely prevented by di etary or intravenous pretreatment with the water-soluble antioxidant v itamin C (venules, 21.4 +/- 11.0 vs. 149.6 +/- 38.7 leukocytes per mm( 2), P < 0.01; arterioles, 8.5 +/- 4.2 vs. 54.3 +/- 21.6 leukocytes per mm(2), P < 0.01; aortas, 0.8 +/- 0.4 vs. 12.4 +/- 5.6 leukocytes per mm(2), P < 0.01; means +/- SD of n = 7 animals, 15 min after CS exposu re). No inhibitory effect was observed by pretreatment of the animals with the lipid-soluble antioxidants vitamin E or probucol. The protect ive effects of vitamin C on CS-induced leukocyte adhesion and aggregat ion were seen at vitamin C plasma levels (55.6 +/- 22.2 mu M, n = 7) t hat can easily be reached in humans by dietary means or supplementatio n, suggesting that vitamin C effectively contributes to protection fro m CS-associated cardiovascular and pulmonary diseases in humans.