A prototypic modified risk tobacco product exhibits reduced effects on chemotaxis and transendothelial migration of monocytes compared with a reference cigarette. (June 2015)

• Record Type: Journal Article
• Authors: van der Toorn, Marco; Frentzel, Stefan; Goedertier, Didier; Peitsch, Manuel; Hoeng, Julia; De Leon, Hector
• Is Part Of: Food and chemical toxicology. Volume 80(2015)
• Page Start: 277
• Page End: 286
• Publication Date: 2015-06
• Subjects: Inflammation -- Transmigration -- THP-1 cell -- Endothelial cell -- Atherosclerosis -- Modified risk tobacco products; 7-AAD 7-aminoactinomycin D -- BSA bovine serum albumin -- CIM cell invasion/migration -- CO carbon monoxide -- CS cigarette smoke -- CXCL12 C-X-C motif ligand 12 -- DNPH dinitrophenylhydrazine -- E-plate electrical impedance plate -- fMLP N-formylmethionyl-leucyl-phenylalanine -- GM-CSF granulocyte-macrophage colony-stimulating factor -- HCAECs human coronary arterial endothelial cells -- HGF hepatocyte growth factor -- ICAM1 intercellular adhesion molecule-1 -- IL-8 interleukin-8 -- LC-MS liquid chromatography-electrospray ionization tandem mass spectrometry -- MCP-1 monocyte chemoattractant protein-1 -- NO nitrogen monoxide -- pMRTP prototypic modified risk tobacco product -- RTCA-DP real-time cell analyzer dual-plate -- SELE E-selectin -- TEM transendothelial migration -- THP-1 human monocytic cell line -- TNF-α tumor necrosis factor-α -- VCAM1 vascular cell adhesion molecule; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2015.03.026
• Languages: English
• ISSNs: 0278-6915

Abstract

Highlights: CXCL12 and a functional monolayer of HCAECs are required for monocytes to differentiate and acquire an adhesive phenotype. Extracts from pMRTP induce less inflammation and migration and are less cytotoxic than those from reference tobacco products. Heating instead of burning tobacco reduces the number and amounts of constituents that are harmful to cardiovascular tissues. Abstract: Monocyte adhesion and migration to the subendothelial space represent critical steps in atherogenesis. Here, we investigated whether extracts from the aerosol of a prototypic modified risk tobacco product (pMRTP), based on heating rather than combusting tobacco, exhibited differential effects on the migratory behavior of monocytes compared with that from the reference cigarette, 3R4F. THP-1 cells, a monocytic cell line, and human coronary arterial endothelial cells (HCAECs) were used to investigate chemotaxis and transendothelial migration (TEM) of monocytes in conventional and impedance-based systems. THP-1 cells migrated through a monolayer of HCAECs in response to C-X-C motif ligand 12 (CXCL12), a chemokine involved in diverse cellular functions including chemotaxis and survival of stem cells. Treatment of THP-1 cells with extracts from 3R4F or pMRTP induced concentration-dependent increases in cytotoxicity (7-aminoactinomycin D), and inflammation (IL-8 and TNF-α). CXCL12-mediated chemotaxis and TEM were decreased in extract-treated THP-1 cells. Extracts from 3R4F were ~21 times more potent than those from pMRTP in all examined endpoints. Extracts from 3R4F and pMRTP induced concentration-dependent responses in assays of inflammation, cytotoxicity, chemotaxis, and TEM. Furthermore, our findings indicate that extracts from a pMRTP are significantly less cytotoxic and induce less inflammation than those from the reference cigarette, 3R4F.