title: Both ICAM-1- and VCAM-1-integrin interactions are important in mediating monocyte adhesion to human saphenous vein.
abstract: Atherosclerosis underlies late occlusion of human saphenous vein (HSV) coronary artery bypass grafts. Monocyte infiltration is implicated, but its mechanisms are unclear given that HSV normally expresses the ICAM-1 but not the VCAM-1 adhesion molecule. To define the mechanisms underlying monocyte adhesion, samples of HSV taken from coronary artery bypass graft patients were co-cultured with human monocytes and adherent monocytes were quantified by immunocytochemistry for CD68 on transverse sections. Pre-treatment of veins with anti-ICAM-1 antibodies reduced monocyte adhesion (monocytes/mm of section) from 7.2 +/- 1.5 to 3.1 +/- 0.7 (p < 0.05, n = 6), but the effect of anti-VCAM-1 was not significant (4.1 +/- 0.7). Paradoxically, pre-treatment of monocytes with either anti-beta(2)-integrins, the counter-receptor of ICAM-1, or anti-alpha(4) integrins, the counter-receptor of VCAM-1, significantly reduced adhesion (1.8 +/- 0.6 and 2.4 +/- 0.7, respectively, p < 0.05). These results were clarified by immunocytochemistry, which confirmed that VCAM-1 expression was absent in harvested vein but was induced in the endothelium during co-culture. Consistent with this, when anti-ICAM-1 or anti-VCAM-1 was present throughout co-culture, either of them reduced adhesion (from 4.2 +/- 0.9 to 2.3 +/- 0.5 and 2.2 +/- 0.4, respectively, p < 0.02, n = 8) and there was no further effect of adding both (2.0 +/- 0.5). These results demonstrate that both ICAM-1/beta(2) and VCAM-1/alpha(4) integrin interactions mediate monocyte adhesion to HSV, possibly as part of a common pathway. These experiments imply that either integrin might be targeted to reduce monocyte infiltration into HSV grafts.
authors.affiliation: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, UK.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Crook
authors.forename: Kay M
authors.initials: KM
authors.lastname: Southgate
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Newby
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D012501:Saphenous Vein / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D018821:CD18 Antigens; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule