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Extracellular survivin up‐regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern
Author(s) -
Mera Simona,
Magnusson Mattias,
Tarkowski Andrej,
Bokarewa Maria
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0507287
Subject(s) - survivin , extracellular , biology , integrin , immunology , inflammation , microbiology and biotechnology , cell adhesion molecule , cd11c , cell adhesion , cancer research , inhibitor of apoptosis , phenotype , receptor , apoptosis , cell , biochemistry , gene , programmed cell death
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 α‐chains of β‐integrins and their ligand ICAM‐1. Survivin‐induced expression of α‐chains of β 2 ‐integrins is regulated by p38 MAPK and PI‐3K but not by the NF‐κB 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.