Shan Huang1, Anna E Engberg2, Nina Jonsson3, Kerstin Sandholm1, Ian A Nicholls4, Tom Eirik Mollnes5, Karin Fromell6, Bo Nilsson6, Kristina N Ekdahl7. 1. Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden. 2. Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Clinical Chemistry, University and Regional Laboratories Region Skåne, Sweden. 3. Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden. 4. Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Chemistry, BMC Uppsala University, Uppsala, Sweden. 5. 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. 6. Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden. 7. 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.
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.
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: C Suffritti; E Tobaldini; R Schiavon; S Strada; L Maggioni; S Mehta; G Sandrone; E Toschi-Dias; M Cicardi; N Montano Journal: Clin Exp Immunol Date: 2017-08-04 Impact factor: 4.330
Authors: Gulaim A Seisenbaeva; Karin Fromell; Vasiliy V Vinogradov; Aleksey N Terekhov; Andrey V Pakhomov; Bo Nilsson; Kristina Nilsson Ekdahl; Vladimir V Vinogradov; Vadim G Kessler Journal: Sci Rep Date: 2017-11-13 Impact factor: 4.379