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

Cell Commun Adhes. 2003 Jan-Feb;10(1):17-26. doi: 10.1080/15419060302065.

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.

MeSH terms

  • Adhesiveness
  • Analysis of Variance
  • Animals
  • Biocompatible Materials / chemistry
  • CD11b Antigen / metabolism
  • CD11b Antigen / physiology*
  • CD18 Antigens / biosynthesis
  • CHO Cells
  • Carbon Compounds, Inorganic / chemistry
  • Cell Adhesion
  • Cell Line
  • Cricetinae
  • Electrochemistry
  • Flow Cytometry
  • Humans
  • Monocytes / cytology*
  • Monocytes / metabolism
  • Peptides / chemistry
  • Semiconductors
  • Silicon Compounds / chemistry
  • Stainless Steel / chemistry*
  • Stents*

Substances

  • Biocompatible Materials
  • CD11b Antigen
  • CD18 Antigens
  • Carbon Compounds, Inorganic
  • Peptides
  • Silicon Compounds
  • Stainless Steel
  • silicon carbide