Forschungsdatenbank PMU-SQQUID

PMU-Autor/inn/en

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.

Useful keywords (using NLM MeSH Indexing)

Adult

Case-Control Studies

Cell Adhesion Molecules/blood

Cell Adhesion Molecules/metabolism*

Cell Membrane/metabolism

Cell Movement/drug effects*

Cell Movement/immunology*

Female

Glatiramer Acetate

Humans

Immunosuppressive Agents/pharmacology*

Leukocytes, Mononuclear/drug effects

Leukocytes, Mononuclear/immunology

Leukocytes, Mononuclear/metabolism

Male

Middle Aged

Multiple Sclerosis/blood

Multiple Sclerosis/immunology*

Multiple Sclerosis/metabolism*

Multiple Sclerosis, Relapsing-Remitting/blood

Multiple Sclerosis, Relapsing-Remitting/immunology

Multiple Sclerosis, Relapsing-Remitting/metabolism

Peptides/pharmacology*

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