title: Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
abstract: BACKGROUND
  Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.
  
  
  METHODS
  Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.
  
  
  RESULTS
  Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.
  
  
  CONCLUSIONS
  A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.
authors.affiliation: Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Clinical Chemistry, University and Regional Laboratories Region Skåne, Sweden.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Engberg
authors.affiliation: Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Jonsson
authors.affiliation: Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sandholm
authors.affiliation: Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Chemistry, BMC Uppsala University, Uppsala, Sweden.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Nicholls
authors.affiliation: Department of Immunology, Oslo University Hospital Rikshopsitalet, and K.G. Jebsen ICR, University of Oslo, Norway; Research Laboratory, Nordland Hospital, Bodø, Norway; Faculty of Health Sciences, University of Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Fromell
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.affiliation: Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden. Electronic address: Kristina.Nilsson_Ekdahl@igp.uu.se.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
mesh_terms: D000327:Adsorption; D000991:Antithrombins / Q000378:metabolism; D001672:Biocompatible Materials; D001777:Blood Coagulation / Q000187:drug effects; D001798:Blood Proteins / Q000737:chemistry; D003167:Complement Activation; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein; D015926:Complement C3a / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D015956:Factor XIIa / Q000378:metabolism; D015945:Factor XIa / Q000378:metabolism; D005898:Glass; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007074:Immunoglobulin G / Q000032:analysis; D007610:Kallikreins / Q000378:metabolism; D010316:Particle Size; D011108:Polymers; D011137:Polystyrenes; D011143:Polyvinyl Chloride; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000991:Antithrombins; D001672:Biocompatible Materials; D001798:Blood Proteins; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines; D006629:Hirudins; D007074:Immunoglobulin G; D011108:Polymers; D011137:Polystyrenes; D011994:Recombinant Proteins; C469952:SERPING1 protein, human; D015926:Complement C3a; D011143:Polyvinyl Chloride; D007610:Kallikreins; D015945:Factor XIa; D015956:Factor XIIa; C083544:lepirudin
keywords: Biomaterials; Complement system; Contact system; FXII; In vitro screening