Effects of cross-linking ICAM-1 on the surface of human vascular smooth muscle cells: induction of VCAM-1 but no proliferation

Objective: Intercellular adhesion molecule (ICAM)-1 is an immunoglobulin-li ke cell adhesion molecule expressed by several cell types, including prolif erating vascular smooth muscle cells (VSMC). Cross-linking ICAM-1 on the su rface of different cell types has previously been shown to cause an increas e in cellular activation within the cytoplasm. Here, our objective was to e xamine events following ligation of ICAM-1 on the surface of human VSMC. Me thods: VSMC were isolated by explant from human pulmonary arteries or aorti c tissue from cardiac transplant donors. ICAM-1 was ligated with monoclonal antibodies, followed by cross-linking with a secondary antibody. Activatio n of signalling pathways, proliferation and expression of a second adhesion molecule, vascular cell adhesion molecule (VCAM)-1 were investigated. Resu lts: ICAM-1 cross-linking caused an increase in activation of extracellular regulated kinase (Erk)-1/-2 and Jun N-terminal kinase (JNK)-1/-2. mRNA and protein for VCAM-1 was observed after ICAM-1 cross-linking, and this was a brogated by addition of an upstream inhibitor of Erk-1/-2, PD98059. No incr ease in cell proliferation was observed. Conclusions: Ligation of ICAM-1 on the surface of vascular smooth muscle cells in vitro, leads to the express ion of adhesion molecules associated with monocyte infiltration, but does n ot contribute to smooth muscle cell proliferation. In vivo, this might lead to prolongation of the inflammatory response within diseased blood vessels , by arresting monocytes within atherosclerotic plaques. (C) 2001 Elsevier Science B.V. All rights reserved.