Activation of Factor

Tobacco glycoprotein (TGP)' is a brown, iron-containing substance of mol wt ca. 18,000 isolated from saline extracts of flue cured tobacco leaves by ammonium sulfate fractionation, chromatography on Sephadex G-25, and continuous flow, preparative electrophoresis on alkaline polyacrylamide gel. 12 of 31 volunteers (6/15 smokers and 6/16 nonsmokers) exhibited immediate cutaneous hypersensitivity reactions characterized by wheal and flare development and local itching when injected intracutaneously with this material. Immunochemically similar material was demonstrated in, and isolated from, cigarette smoke. Antigenically cross-reactive material was also demonstrated in eggplants, green peppers, potatoes, and tomatoes, which like tobacco, are members of the family Solanaceae (1). The brown color, molecular weight, amino acid analysis, iron content, and presence of carbohydrate moiety in TGP correspond to that of an iron-proteinchlorogenic acid-rutin complex in cured tobacco leaves first reported by Wright et al. (2). Since rutin is chemically similar to quercetin, a substance known to activate factor XII (3), we examined whether TGP isolated from cured Virginia Bright tobacco leaves or from cigarette smoke condensate was capable of activating factor XII in human blood plasma. In experiments described below we demonstrated that TGP derived from cured tobacco leaves or from cigarette smoke condensate contained rutin or a rutin-like substance and activated factor XII in samples of human plasma resulting in the generation of clotting activity, fibrinolytic activity, and kinin activity.