I Giunzioni1, A Bonomo1, E Bishop2, S Castiglioni1, A Corsini1, S Bellosta3. 1. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy. 2. British American Tobacco Group Research & Development, Southampton, UK. 3. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy. Electronic address: stefano.bellosta@unimi.it.
Abstract
OBJECTIVE: Circulating monocytes adhere to the endothelium and migrate into the intima contributing to atherosclerotic plaque growth. Cigarette smoke is a risk factor for atherosclerosis, but it is not completely known how it affects monocyte behavior in atherogenesis. METHODS: We studied the effects of cigarette smoke condensate (CSC) on human monocytes (HM) chemotaxis and transmigration through an endothelial cell (EC) monolayer. RESULTS: Pre-treatment with CSC caused a decrease in HM chemotaxis and transmigration (-55% and -18% vs control, p < 0.05, respectively), paralleled by a reduced expression of Rac 1 GTPase. On the contrary, direct exposure of both HM and EC to CSC increased (+23% vs control, p < 0.05) HM transmigration, paralleled by a strong stimulation of VCAM1 and ICAM1 expression by ECs, and by a slight increase in monocyte integrin expression. An enhancement of monocyte transmigration was obtained after the exposure of both HM and EC to medium conditioned by HM previously incubated with CSC (+265% vs control, p < 0.001). CSC showed a stimulatory effect on the expression by HM of TLR4, MCP1, IL8, IL1beta, and TNFalfa, which was ablated by pre treatment with PDTC. Incubation with neutralizing antibodies against both MCP1 or IL8 completely abolished the CSC-conditioned medium induced HM transmigration. CONCLUSIONS: CSC induces HM to release chemotactic factor(s), which amplify the recruitment and transmigration of inflammatory cells through EC, but CSC may also reduce HM migratory capacity. Therefore, exposure to CSC affects monocyte behavior and interaction with the endothelium, thus potentially facilitating and/or further aggravating the atherogenic process.
OBJECTIVE: Circulating monocytes adhere to the endothelium and migrate into the intima contributing to atherosclerotic plaque growth. Cigarette smoke is a risk factor for atherosclerosis, but it is not completely known how it affects monocyte behavior in atherogenesis. METHODS: We studied the effects of cigarette smoke condensate (CSC) on human monocytes (HM) chemotaxis and transmigration through an endothelial cell (EC) monolayer. RESULTS: Pre-treatment with CSC caused a decrease in HM chemotaxis and transmigration (-55% and -18% vs control, p < 0.05, respectively), paralleled by a reduced expression of Rac 1 GTPase. On the contrary, direct exposure of both HM and EC to CSC increased (+23% vs control, p < 0.05) HM transmigration, paralleled by a strong stimulation of VCAM1 and ICAM1 expression by ECs, and by a slight increase in monocyte integrin expression. An enhancement of monocyte transmigration was obtained after the exposure of both HM and EC to medium conditioned by HM previously incubated with CSC (+265% vs control, p < 0.001). CSC showed a stimulatory effect on the expression by HM of TLR4, MCP1, IL8, IL1beta, and TNFalfa, which was ablated by pre treatment with PDTC. Incubation with neutralizing antibodies against both MCP1 or IL8 completely abolished the CSC-conditioned medium induced HM transmigration. CONCLUSIONS: CSC induces HM to release chemotactic factor(s), which amplify the recruitment and transmigration of inflammatory cells through EC, but CSC may also reduce HM migratory capacity. Therefore, exposure to CSC affects monocyte behavior and interaction with the endothelium, thus potentially facilitating and/or further aggravating the atherogenic process.
Authors: Brian K Nordskog; Buddy G Brown; Kristin M Marano; Leanne R Campell; Bobbette A Jones; Michael F Borgerding Journal: Inhal Toxicol Date: 2015-03-19 Impact factor: 2.724
Authors: Leonardo Sandrini; Laura Castiglioni; Patrizia Amadio; José Pablo Werba; Sonia Eligini; Susanna Fiorelli; Marta Zarà; Silvia Castiglioni; Stefano Bellosta; Francis S Lee; Luigi Sironi; Elena Tremoli; Silvia Stella Barbieri Journal: Cells Date: 2020-04-27 Impact factor: 6.600