title: Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes.
abstract: Reduction of harmful constituents by heating rather than combusting tobacco is a promising new approach to reduce harmful effects associated with cigarette smoking. We investigated the effect from a new candidate modified risk tobacco product, the tobacco heating system (THS) 2.2, on the migratory behavior of monocytes in comparison with combustible 3R4F reference cigarettes. The monocytic cell line (THP-1) and human coronary arterial endothelial cells (HCAECs) were used to analyze chemotaxis and transendothelial migration (TEM). To assess the influence of aerosol extract from THS2.2 and smoke extract from 3R4F on toxicity and inflammation, flow cytometry and ELISA assays were performed. The results show that treatment of THP-1 cells with extract from 3R4F or THS2.2 induced concentration-dependent increases in cytotoxicity and inflammation. The inhibitory effects of THS2.2 extract for chemotaxis and TEM were ∼18 times less effective compared to 3R4F extract. Furthermore, extract from 3R4F or THS2.2 induced concentration-dependent decreases in the integrity of HCAEC monolayer. For all examined endpoints, the extract from 3R4F showed more than one order of magnitude stronger effects than that from THS2.2 extract. These data indicate the potential of a heat not burn tobacco product to reduce the risk for cardiovascular disease compared to combustible cigarettes.
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Marco.vanderToorn@pmi.com.
authors.forename: Marco
authors.initials: M
authors.lastname: van der Toorn
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Stefan.Frentzel@pmi.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frentzel
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: hdeleon68@hotmail.com.
authors.forename: Hector
authors.initials: H
authors.lastname: De Leon
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Didier.Goedertier@pmi.com.
authors.forename: Didier
authors.initials: D
authors.lastname: Goedertier
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Manuel.Peitsch@pmi.com.
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Julia.Hoeng@pmi.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
mesh_terms: D000336:Aerosols / Q000737:chemistry* / Q000633:toxicity*; D002454:Cell Differentiation; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects*; D062789:Tobacco Products / Q000032:analysis*
chemical_list: D000336:Aerosols; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: Atherosclerosis; Endothelial cells; Modified risk tobacco product; THP-1 cells; Tobacco-heating system; Transendothelial migration