Mechanism of complement activation during extracorporeal blood-biomaterial interaction: effects of heparin coated and uncoated surfaces.
In vitro studies with miniaturized rotating circuits and heparinized human blood, as well as long-term extracorporeal membrane oxygenation with either heparin coated (HBS) or uncoated surfaces connected to adult sheep, were performed comparing the impact on complement activation in blood and on surfaces. Analysis of surface bound complement proteins revealed significantly reduced binding of activated C3 and C5b-9 to HBS in vitro, compared with uncoated surfaces, which was probably due to more HBS bound complement inhibitors (C1-Inhibitor, factor H) being present. This was reflected by significantly reduced activation of the alternative pathway (C3bBbP) and terminal complex (SC5b-9) by HBS but slightly increased levels of classic pathway complex (C1rs-C1-inhibitor). These results were confirmed during in vivo study by analysis of hemolytic complement function, activation specific C3 derived split products, and surface bound complement proteins. Increased binding of complement regulators to HBS appears to effectively reduce complement activation by biomaterials, leading to improved long-term biocompatibility.
Kopp
Ruedger
R
Institute of Physiology, University Hospital Aachen, Germany.
Mottaghy
Khosrow
K
Kirschfink
Michael
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000187:drug effects; D005112:Extracorporeal Circulation; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D010976:Platelet Count; D012756:Sheep
D000925:Anticoagulants; D020099:Coated Materials, Biocompatible; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D000990:Antithrombin III; D005340:Fibrinogen; D006493:Heparin