Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking

被引:135
作者
Lehr, HA
Weyrich, AS
Saetzler, RK
Jurek, A
Arfors, KE
Zimmerman, GA
Prescott, SM
McIntyre, TM
机构
[1] UNIV UTAH, NORA ECCLES HARRISON CVRTI, DEPT MED, SALT LAKE CITY, UT 84112 USA
[2] UNIV MAINZ, INST PATHOL, D-6500 MAINZ, GERMANY
[3] TEMPLE UNIV, DEPT PHYSIOL, PHILADELPHIA, PA 19122 USA
[4] EXPT MED INC, PRINCETON, NJ 08540 USA
[5] UNIV UTAH, HUNTSMAN CANC INST, DEPT MED, SALT LAKE CITY, UT 84112 USA
[6] UNIV UTAH, DEPT EXPT PATHOL, SALT LAKE CITY, UT 84112 USA
关键词
leukocytes; monocytes; blood platelets; endothelium; chemokines;
D O I
10.1172/JCI119417
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1 alpha. Both events were blocked by a PAF receptor antagonist. Similarly, blocking the PAF receptor in vivo blocked smoke-induced leukocyte aggregation and pavementing along the vascular wall. Dietary supplementation with the antioxidant vitamin C prevented the accumulation of PAF-like lipids, and it prevented cigarette smoke-induced leukocyte adhesion to the vascular wall and formation of leukocyte-platelet aggregates. This is the first in vivo demonstration of inflammatory phospholipid oxidation products and it suggests a molecular mechanism coupling cigarette smoke with rapid inflammatory changes. Inhibition of PAF-like lipid formation and their intravascular sequela by vitamin C suggests a simple dietary means to reduce smoking-related cardiovascular disease.
引用
收藏
页码:2358 / 2364
页数:7
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