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Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
Biomaterials. 2016 Jan; 77:111-9.B

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+Show Affiliations

Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden.Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Clinical Chemistry, University and Regional Laboratories Region Skåne, Sweden.Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden.Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden.Linnæus University Center of Biomaterials Chemistry, Linnæus University, Kalmar, Sweden; Department of Chemistry, BMC Uppsala University, Uppsala, Sweden.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.Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden.Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Sweden.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26584351

Citation

Huang, Shan, et al. "Reciprocal Relationship Between Contact and Complement System Activation On Artificial Polymers Exposed to Whole Human Blood." Biomaterials, vol. 77, 2016, pp. 111-9.
Huang S, Engberg AE, Jonsson N, et al. Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood. Biomaterials. 2016;77:111-9.
Huang, S., Engberg, A. E., Jonsson, N., Sandholm, K., Nicholls, I. A., Mollnes, T. E., Fromell, K., Nilsson, B., & Ekdahl, K. N. (2016). Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood. Biomaterials, 77, 111-9. https://doi.org/10.1016/j.biomaterials.2015.10.067
Huang S, et al. Reciprocal Relationship Between Contact and Complement System Activation On Artificial Polymers Exposed to Whole Human Blood. Biomaterials. 2016;77:111-9. PubMed PMID: 26584351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood. AU - Huang,Shan, AU - Engberg,Anna E, AU - Jonsson,Nina, AU - Sandholm,Kerstin, AU - Nicholls,Ian A, AU - Mollnes,Tom Eirik, AU - Fromell,Karin, AU - Nilsson,Bo, AU - Ekdahl,Kristina N, Y1 - 2015/11/09/ PY - 2015/07/31/received PY - 2015/10/22/revised PY - 2015/10/26/accepted PY - 2015/11/20/entrez PY - 2015/11/20/pubmed PY - 2016/10/19/medline KW - Biomaterials KW - Complement system KW - Contact system KW - FXII KW - In vitro screening SP - 111 EP - 9 JF - Biomaterials JO - Biomaterials VL - 77 N2 - 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. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/26584351/Reciprocal_relationship_between_contact_and_complement_system_activation_on_artificial_polymers_exposed_to_whole_human_blood_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(15)00877-7 DB - PRIME DP - Unbound Medicine ER -