Abstract
Conditional on preparation techniques, stem cell products contain a considerable amount of platelets. But platelets are the major source of soluble CD40 ligand (sCD40L) in the blood. It has been demonstrated that CD40L is cleaved from the surface of activated platelets. So it can be expected that sCD40L accumulates in stem cell products reaching levels above the physiological range.
Therefore sCD40L concentrations were observed in peripheral blood samples and in the respective stem cell products of allogenic stem cell donors (peripheral stem cell apheresis or bone marrow) as well as of patients undergoing autologous stem cell apheresis. sCD40L concentrations were normally determined by different ELISA techniques.
In stem cell products, sCD40L concentrations were manifold elevated (range from 1,239 to 3,839 pg/mL) in comparison to concentrations of peripheral blood samples (range from 43 to 321 pg/mL). Experimentally, using MMP-9-, MMP-2- and MMP-2/9-inhibitors sCD40L release by platelets could be inhibited up to 90% of the control values. During autologous stem cell apheresis, the decrease in platelet count from 95,070/μL ± 58,234/μL at the beginning to 54,638/μL ± 26,944/μL at the end of the procedure was accompanied by a significant lowering of sCD40L concentrations in peripheral blood samples from 239 pg/mL ± 139 pg/mL to 126 pg/mL ± 71 pg/mL (dependent on platelet count, linearly correlated, r = 0.95).
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. In addition, during stem cell apheresis sCD40L concentrations in peripheral blood were mainly influenced by alterations of platelet count.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Andre P, Nannizzi-Alaimo L, Prasad SK, Phillips DR (2002a) Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation 106:896–899
Andre P, Prasad KS, Denis CV, He M, Papalia JM, Hynes RO, Phillips DR, Wagner DD (2002b) CD40L Stabilizes arterial thrombi by a beta3 integrin–dependent mechanism. Nat Med 8:247–252
Aye MT, Palmer DS, Giulivi A, Hashemi S (1995) Effect of filtration of platelet concentrates on the accumulation of cytokines and platelet release factors during storage. Transfusion 35:117–124
Blumberg N, Gettings KF, Turner C, Heal JM, Phipps RP (2006) An association of soluble CD40 ligand (CD154) with adverse reactions to platelet transfusions. Transfusion 46:1813–1821
Chew M, Rahman M, Ihrman L, Erson A, Zhang S, Thorlacius H (2010) Soluble CD40L (CD154) is increased in patients with shock. Inflamm Res 59:979–982
Choi WS, Jeon OH, Kim DS (2010) CD40 ligand shedding is regulated by interaction between matrix metalloproteinase-2 and platelet integrin alpha(IIb)beta(3). J Thromb Haemost 8:1364–1371
Cognasse F, Payrat JM, Corash L, Osselaer JC, Garraud O (2008) Platelet components associated with acute transfusion reactions: the role of platelet-derived soluble CD40 ligand. Blood 112:4779–4780
Domanovic D, Wozniak G, Cernelc P, Samardzija M, Balen-Marunic S, Rozman P (2005) Matrix metalloproteinase-9 and cell kinetics during the collection of peripheral blood stem cells by leukapheresis. Transfus Apher Sci 33:37–45
Kaufman J, Spinelli SL, Schultz E, Blumberg N, Phipps RP (2007) Release of biologically active CD154 during collection and storage of platelet concentrates prepared for transfusion. J Thromb Haemost 5:788–796
Khan SY, Kelher MR, Heal JM, Blumberg N, Boshkov LK, Phipps R, Gettings KF, McLaughlin NJ, Silliman CC (2006) Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury. Blood 108:2455–2462
Mach F, Schonbeck U, Sukhova GK, Bourcier T, Bonnefoy JY, Pober JS, Libby P (1997) Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. Proc Natl Acad Sci U S A 94:1931–1936
Menchen L, Marin-Jimenez I, Arias-Salgado EG, Fontela T, Hernandez-Sampelayo P, Rodriguez MC, Butta NV (2009) Matrix metalloproteinase 9 is involved in Crohn’s disease-associated platelet hyperactivation through the release of soluble CD40 ligand. Gut 58:920–928
Phipps RP, Kaufman J, Blumberg N (2001) Platelet derived CD154 (CD40 ligand) and febrile responses to transfusion. Lancet 357:2023–2024
Reinboldt S, Wenzel F, Rauch BH, Hohlfeld T, Grandoch M, Fischer JW, Weber AA (2009) Preliminary evidence for a matrix metalloproteinase-2 (MMP-2)-dependent shedding of soluble CD40 ligand (sCD40L) from activated platelets. Platelets 20:441–444
Wenzel F, Baertl A, Zimmermann N, Hohlfeld T, Giers G, Oldenburg J, Assert R (2008) Different behaviour of soluble CD40L concentrations can be reflected by variations of preanalytical conditions. Clin Hemorheol Microcirc 39:417–422
Wenzel F, Gunther W, Baertl A, Lasshofer R, Rox J, Fischer JC, Giers G (2011a) Comparison of soluble CD40L concentrations and release capacities in apheresis and prestorage pooled platelet concentrates. Clin Hemorheol Microcirc 47:269–278
Wenzel F, Gunther W, Rox JM, Fischer JC, Giers G (2011b) Soluble CD40 ligand in stem cell products of autologous donors. Transfusion 51:226–227
Woods I, Tawab-Amiri A, Byrne K, Sabatino M, Stroncek DF (2010) Pilot analysis of cytokines levels in stored granulocyte-colony-stimulating factor-mobilized peripheral blood stem cell concentrates. Transfusion 50:2011–2015
Zirlik A, Maier C, Gerdes N, MacFarlane L, Soosairajah J, Bavendiek U, Ahrens I, Ernst S, Bassler N, Missiou A, Patko Z, Aikawa M, Schonbeck U, Bode C, Libby P, Peter K (2007) CD40 ligand mediates inflammation independently of CD40 by interaction with Mac-1. Circulation 115:1571–1580
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Wenzel, F. (2014). Soluble CD40L in Stem Cell Products. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 12. Stem Cells and Cancer Stem Cells, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8032-2_21
Download citation
DOI: https://doi.org/10.1007/978-94-017-8032-2_21
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-017-8031-5
Online ISBN: 978-94-017-8032-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)