title: Cigarette smoke condensate affects monocyte interaction with endothelium.
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.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Giunzioni
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonomo
authors.affiliation: British American Tobacco Group Research & Development, Southampton, UK.
authors.forename: E
authors.initials: E
authors.lastname: Bishop
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Castiglioni
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corsini
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy. Electronic address: stefano.bellosta@unimi.it.
authors.forename: S
authors.initials: S
authors.lastname: Bellosta
mesh_terms: D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; C573420:ICAM1 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; C107953:RAC1 protein, human; D012906:Smoke; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D020830:rac1 GTP-Binding Protein
keywords: Cigarette smoke; Endothelium; Macrophages; Monocytes; Transmigration