Article: article from journal or magazin.
Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.
Journal of Clinical Investigation
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-1alpha. 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.
Animals, Antioxidants/pharmacology, Ascorbic Acid/pharmacology, Azepines/pharmacology, Blood Platelets/drug effects, Blood Platelets/physiology, Cell Adhesion, Cell Aggregation, Chemokine CCL4, Cricetinae, Humans, Interleukin-8/blood, Macrophage Inflammatory Proteins/blood, Monocytes/drug effects, Monocytes/physiology, Neutrophils/drug effects, Neutrophils/physiology, Platelet Activating Factor/analogs & derivatives, Platelet Activating Factor/antagonists & inhibitors, Platelet Aggregation/drug effects, Platelet Aggregation Inhibitors/pharmacology, Platelet Membrane Glycoproteins/antagonists & inhibitors, Platelet Membrane Glycoproteins/physiology, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Reference Values, Smoking/blood, Time Factors, Triazoles/pharmacology
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