title: Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.
abstract: An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.
authors.affiliation: Department of Neurology, Paracelsus Medical University, Salzburg, Austria. j.sellner@salk.at
authors.forename: J
authors.initials: J
authors.lastname: Sellner
authors.forename: W
authors.initials: W
authors.lastname: Koczi
authors.forename: A
authors.initials: A
authors.lastname: Harrer
authors.forename: K
authors.initials: K
authors.lastname: Oppermann
authors.forename: E
authors.initials: E
authors.lastname: Obregon-Castrillo
authors.forename: G
authors.initials: G
authors.lastname: Pilz
authors.forename: P
authors.initials: P
authors.lastname: Wipfler
authors.forename: S
authors.initials: S
authors.lastname: Afazel
authors.forename: E
authors.initials: E
authors.lastname: Haschke-Becher
authors.forename: E
authors.initials: E
authors.lastname: Trinka
authors.forename: J
authors.initials: J
authors.lastname: Kraus
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate
keywords: adhesion molecule; glatiramer-acetate; immunomodulation; multiple sclerosis; transmigration