title: Cardiopulmonary bypass induces release of soluble CD40 ligand.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) is known to induce platelet activation, thrombosis, thrombocytopenia, and a systemic inflammatory response. It is known that CD40 ligand (CD40L) exists in platelets, that a soluble form of this protein (sCD40L) is released on platelet activation, that platelets are the primary source of sCD40L in blood, and that sCD40L is involved in thrombosis and inflammation. The present study was designed to determine whether sCD40L is released during CPB. Methods and Results- Blood was obtained from patients undergoing CPB-requiring surgery and analyzed for sCD40L, interleukin-6, and platelet factor 4 and beta-thromboglobulin (markers of platelet activation). Platelets were also isolated and analyzed for their levels of CD40L. Plasma levels of sCD40L increased >1.7-fold (from 0.29 to 0.51 ng/mL, P=0.001) within 1 hour on CPB and increased further to 3.7-fold (to 1.08 ng/mL, P=0.03) 2 hours after the procedure. Half of the released sCD40L was cleared in 2 hours, which allowed the sCD40L to return to approximately baseline levels 8 hours after the procedure. The platelet content of CD40L was decreased by 40% (2.675 to 1.64 ng/10(8) platelets, P=0.001) 1 hour after initiation of CPB and was similar to that observed for platelet factor 4 and beta-thromboglobulin. Interleukin-6, a marker of inflammation, also increased during CPB.
  
  
  CONCLUSIONS
  The present study demonstrates that CPB causes an increase in the concentration of plasma sCD40L. The corresponding decrease in platelet CD40L suggests that this prothrombotic and proinflammatory protein was derived primarily from platelets and may contribute to the thrombotic and inflammatory complications associated with CPB.
authors.affiliation: COR Therapeutics, South San Francisco, California, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nannizzi-Alaimo
authors.forename: Mark H
authors.initials: MH
authors.lastname: Rubenstein
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Alves
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Leong
authors.forename: David R
authors.initials: DR
authors.lastname: Phillips
authors.forename: Herman K
authors.initials: HK
authors.lastname: Gold
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry; D023201:CD40 Ligand / Q000032:analysis / Q000097:blood*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D008297:Male; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000032:analysis; D013927:Thrombosis / Q000209:etiology; D001620:beta-Thromboglobulin / Q000032:analysis
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D001620:beta-Thromboglobulin; D023201:CD40 Ligand; D010978:Platelet Factor 4