title: Differential effect of heparin coating and complement inhibition on artificial surface-induced eicosanoid production.
abstract: BACKGROUND
  Contact between blood and artificial surfaces induces an inflammatory response including activation of leukocytes and platelets, as well as complement and other plasma cascade systems. In the present study we investigated the roles of complement and surface modification in polyvinyl chloride-induced synthesis of eicosanoids (arachidonic acid metabolites).
  
  
  METHODS
  Human whole blood was incubated in rotating loops of polyvinyl chloride or heparin-coated polyvinyl chloride tubing for 4 hours. Plasma concentrations of the eicosanoids leukotriene B4, prostaglandin E2 and thromboxane B2 were quantified.
  
  
  RESULTS
  Polyvinyl chloride induced a substantial increase in leukotriene B4, prostaglandin E2, and thromboxane B2. Inhibition of complement activation by the complement factor 3 binding peptide compstatin or blockade of the complement factor 5a receptor with a specific antagonist significantly and specifically inhibited the synthesis of leukotriene B4, whereas thromboxane B2 and prostaglandin E2 synthesis were apparently complement independent. The increase in all three mediators was significantly reduced by the heparin coating. Indomethacin abolished the increase of the cyclooxygenase products prostaglandin E2 and thromboxane B2, but had no effect on the increase of the lipoxygenase product leukotriene B4, consistent with the specificity of indomethacin for the cyclooxygenase and confirming the specificity of complement inhibition.
  
  
  CONCLUSIONS
  Polyvinyl chloride-induced increase in all three eicosanoids was attenuated by heparin coating, whereas complement inhibition selectively reduced the synthesis of leukotriene B4.
authors.affiliation: Department of Medicine, Nordland Hospital, Bodø and University of Tromsø, Tromsø, Norway. knut.lappegard@nlsh.no
authors.forename: Knut Tore
authors.initials: KT
authors.lastname: Lappegård
authors.forename: Johan
authors.initials: J
authors.lastname: Riesenfeld
authors.forename: Ole-Lars
authors.initials: OL
authors.lastname: Brekke
authors.forename: Grethe
authors.initials: G
authors.lastname: Bergseth
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D003169:Complement Inactivator Proteins / Q000187:drug effects*; D015232:Dinoprostone / Q000096:biosynthesis*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis*
chemical_list: D003169:Complement Inactivator Proteins; D007975:Leukotriene B4; D013929:Thromboxane B2; D006493:Heparin; D015232:Dinoprostone