Influence of GCSF stimulation on sCD40L release kinetic

Abstract

It has been demonstrated by in vitro experiments using inhibitors that CD40L is cleaved from the surface of activated platelets by matrix-metalloproteinases (MMP). Additionally, after granulocyte colony stimulating factor (GCSF) activation of peripheral stem cell donors a MMP elevation is induced, and stem cell products contain a considerable amount of platelets. Therefore stem cell donations (peripheral stem cell apheresis (PBSC) as well as bone marrow (BM) donation) were used as an in vivo model to observe alterations of the sCD40L release kinetic and its effects on the respective stem cell products. AND METHODS: The study included twelve healthy stem cell donors (PBSC n =6 , BMn = 6). sCD40L concentrations, relative MMP activities and blood cell compositions were determined in peripheral blood as well as in the respective stem cell products before, during and after donation and/or during cell product storage. RESULTS: In stem cell products, sCD40L concentrations were manifold elevated (range from 1121 to 4123 pg/mL) in comparison to concentrations of peripheral blood samples (range from 39 to 334 pg/mL). Dependent on storage duration a sCD40L accumulation in the products could be observed. MMP concentrations were elevated by GCSF stimulation and resulted in an about 2-fold increase of sCD40L release kinetic. In parallel, MMP concentrations were increased in the stem cell products (PBSC as well as BM products). In the peripheral blood of PBSC donors, the sCD40L concentration decreased after apheresis in correlation to a decrease in platelet count. CONCLUSION: As known from platelet concentrates, an accumulation of sCD40L could also be observed in stem cell products pointing out the importance of sCD40L release by platelets. Stem cell products showed elevated MMP concentrations compared to peripheral blood and additionally during stem cell apheresis, sCD40L release kinetic is accelerated by MMP elevation.