Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern.

• Rheumatoid arthritis (RA) is an autoimmune disease with joints as a principal target of inflammation. We have shown recently that the extracellular expression of the antiapoptotic protein survivin is associated with a destructive course of RA. Here, we address the potential impact of extracellular survivin on peripheral blood leukocytes (PBL). The binding of survivin to the surface of human PBL as well as the expression of adhesion molecules were assessed by FACS. The expression of adhesion molecules on leukocytes as a function of circulating survivin was analyzed in blood of 24 patients with RA and compared with eight healthy individuals. We show that extracellular survivin expresses immunomodulatory properties. It binds to the surface of the majority of granulocytes and a significant part of lymphocytes and monocytes inducing the activation of alpha-chains of beta-integrins and their ligand ICAM-1. Survivin-induced expression of alpha-chains of beta 2-integrins is regulated by p38 MAPK and PI-3K but not by the NF-kappaB signaling pathway. Clinical relevance of our findings is supported by the in vivo association of high circulating survivin levels with an increased expression of CD11c on monocytes and granulocytes in RA patients. The results of our study demonstrate that extracellular survivin affects the phenotype of leukocytes having a possible impact on homing of inflammatory cells during arthritis.

Nyckelord

1-Phosphatidylinositol 3-Kinase

immunology

Antigens

CD18

biosynthesis

drug effects

immunology

Arthritis

Rheumatoid

blood

diagnosis

immunology

Cell Adhesion Molecules

drug effects

immunology

Extracellular Space

metabolism

Humans

Leukocytes

drug effects

immunology

Microtubule-Associated Proteins

biosynthesis

immunology

pharmacology

Neoplasm Proteins

biosynthesis

immunology

pharmacology

Recombinant Proteins

biosynthesis

immunology

pharmacology

Signal Transduction

immunology

Up-Regulation

drug effects

immunology

p38 Mitogen-Activated Protein Kinases

immunology

beta(2)-integrins; survivin; p38; inflammation; rheumatoid arthritis

MEDICINE

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)