Extracts of smokeless tobacco induce pro-inflammatory changes in cultured human vascular endothelial cells

Habitual use of smokeless tobacco leads to accumulation of inflammatory leu kocytes at the site of placement, which may contribute to tissue damage. Re cruitment of leukocytes is facilitated by the endothelial lining of blood v essels, which can be activated to express adhesion molecules and to produce chemoattractants. The ability of aqueous extracts of chewing tobacco, dry snuff, and moist snuff to stimulate such changes was investigated using cul tured human umbilical vein endothelial cells (HUVEC). All three extracts ca used HUVEC to express the adhesion molecule E-selectin and to produce the c hemokines interleukin-8 and monocyte chemoattractant protein-1. Neutrophils migrated avidly across HUVEC monolayers that had been previously exposed t o the extracts, whereas migration across unstimulated monolayers was neglig ible. The smokeless tobacco extracts contained relatively high concentratio ns of bacterial lipopolysaccharide (LPS). Although LPS appeared to be the m ajor stimulatory component in extracts of chewing tobacco, it accounted for only part of the activity found in extracts of moist and dry snuffs. These observations suggest that smokeless tobacco may induce inflammatory change s in vivo by activating endothelium in a manner that promotes recruitment o f leukocytes. (C) 2000 Elsevier Science B.V. All rights reserved.