Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 68
EXTRACELLULAR SURVIVIN UPREGULATES ADHESION MOLECULES ON
THE SURFACE OF LEUKOCYTES CHANGING THEIR REACTIVITY PATTERN
Simona Mera, Mattias Magnusson, Andrej Tarkowski, and Maria Bokarewa
Department of Rheumatology and Inflammation Research, Sahlgrenska University
Hospital, Göteborg, Sweden
Background. Rheumatoid arthritis (RA) is an autoimmune disease with joints as a principal
target of inflammation. We have recently shown that the extracellular presence of antiapoptotic
protein survivin was associated with unfavourable, i.e. destructive course of RA.
Here we addressed the effects of extracellular survivin on peripheral leukocytes.
Methods. Human peripheral blood leukocytes were cultured with and without recombinant
survivin and assessed for the surface binding of survivin and the expression of adhesion
molecules. The intracellular expression of survivin in non-activated human leukocytes was
determined. Finally, the expression of adhesion molecules on leukocytes as a function of
circulating survivin was analysed in blood of 24 patients with RA and compared to healthy
individuals.
Results. We found that the anti-apoptotic protein survivin expresses immuno-modulatory
properties when released extracellularly. It binds to a 47% of neutrophils inducing the
activation of #2-integrins and their ligand, ICAM-1. Survivin also binds to lymphocytes
inducing the expression of L-selectin. Survivin-induced expression of #2-integrins could be
abolished by the inhibitors of NFkB (parthenolide), PI3-kinase (LY294002), but not by MAPkinase
inhibitors (PD98059, SB203580). Clinical relevance of our findings is proved by the in
vivo association of extracellular survivin with an increased expression of CD11c on blood
monocytes and neutrophils in RA patients.
Conclusion. The results of our study demonstrate that extracellular survivin affects the
function of leukocytes having possible impact on inflammatory responses during arthritis.
- 401 -