title: Adhesion of monocytes to medical steel as used for vascular stents is mediated by the integrin receptor Mac-1 (CD11b/CD18; alphaM beta2) and can be inhibited by semiconductor coating.
abstract: Implantation of stents into stenosed arteries helps to restore normal blood flow in ischemic organs. However, limited biocompatibility of the applied medical steel can cause acute thrombosis and long-term restenosis. Adhesion of monocytes to stent metal may participate in those acute and long-term complications of stent placement. Based on described prominent electrochemical properties of the interaction between the monocyte integrin receptor Mac-1 and its various ligands, we hypothesized, that this receptor is a central mediator of monocyte adhesion to stent metal and that semiconductor coating of medical steel reduces monocyte adhesion. Adhesion of monocytes on L-316 stainless steel was directly evaluated by light microscopy. Mac-1 could be identified as mediator of monocyte adhesion, since cell adhesion could be blocked by anti-Mac-1-antibodies, including the cross-reacting anti-GPIIb/IIIa antibody fragment abciximab. To further prove the central role of Mac-1, two CHO cell lines were generated expressing recombinant Mac-1 either as wild type, resulting in a low affinity receptor, or mutant with a GFFKR deletion of the alpha(M) subunit, resulting in a high affinity receptor. Indeed, adhesion was specific for Mac-1 and dependent on the affinity state of this integrin. Finally, we could demonstrate that Mac-1-mediated adhesion of monocytes to stents can be significantly inhibited by silicon carbide coating of the stent metal. In conclusion, the integrin Mac-1 and its affinity state could be identified as major mediators of monocyte adhesion on medical steel. As therapeutic strategies, the blockade of Mac-1 by antibodies or silicon carbide coating of steel inhibits monocyte adhesion on stents.
authors.affiliation: Department of Cardiology and Angiology, University of Freiburg, Freiburg, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Schuler
authors.forename: Dawit
authors.initials: D
authors.lastname: Assefa
authors.forename: Jari
authors.initials: J
authors.lastname: Ylänne
authors.forename: Nicole
authors.initials: N
authors.lastname: Basler
authors.forename: Manfred
authors.initials: M
authors.lastname: Olschewski
authors.forename: Ingo
authors.initials: I
authors.lastname: Ahrens
authors.forename: Thomas
authors.initials: T
authors.lastname: Nordt
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000268:Adhesiveness; D000704:Analysis of Variance; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D039481:CD11b Antigen / Q000378:metabolism / Q000502:physiology*; D018821:CD18 Antigens / Q000096:biosynthesis; D016466:CHO Cells; D017554:Carbon Compounds, Inorganic / Q000737:chemistry; D002448:Cell Adhesion; D002460:Cell Line; D006224:Cricetinae; D004563:Electrochemistry; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D012666:Semiconductors; D017655:Silicon Compounds / Q000737:chemistry; D013193:Stainless Steel / Q000737:chemistry*; D015607:Stents
chemical_list: D001672:Biocompatible Materials; D039481:CD11b Antigen; D018821:CD18 Antigens; D017554:Carbon Compounds, Inorganic; D010455:Peptides; D017655:Silicon Compounds; D013193:Stainless Steel; C022088:silicon carbide