BACKGROUND: Exposure of blood to artificial surfaces, as in cardiopulmonary bypass, induces an inflammatory response involving complement, leukocyte and platelet activation. To elucidate the specific role of complement in this process, studies were performed on blood circulated in polyvinyl chloride tubing in the absence and presence of complement inhibitors. Parallel experiments were performed with heparin-coated polyvinyl chloride tubing, which is known to prevent complement and cell activation. METHODS: A novel experimental model was used, based on human whole blood anticoagulated with lepirudin. Complement activation products, myeloperoxidase, lactoferrin, and thrombospondin were quantified in enzyme immunoassays. Leukocyte CD11b expression and leukocyte-platelet conjugates were detected by flow cytometry. RESULTS: Increased levels of C3 activation products, alternative pathway convertase, and the terminal SC5b-9 complex, combined with unchanged levels of C1rs-C1-inhibitor complexes and marginal changes in C4 activation demonstrated that complement was activated through the alternative pathway. Granulocyte and monocyte CD11b expression and granulocyte-platelet conjugate formation were efficiently attenuated by blocking either factor D, C3, C5, or C5a receptor. In contrast, monocyte-platelet conjugate formation and release of myeloperoxidase, lactoferrin, and thrombospondin were not reduced by complement inhibition. Heparin-coated polyvinyl chloride tubing efficiently reduced all inflammatory markers studied, except for C1rs-C1-inhibitor complexes, which increased, consistent with the enhancing effect of heparin on C1-inhibitor function. This effect did not, however, reduce fluid-phase classic pathway activation induced by heat-aggregated immunoglobulin G. CONCLUSIONS: Leukocyte and platelet activation in response to artificial materials occur by mechanisms that vary in their dependence on complement. Heparin coating precludes both the complement-dependent and complement-independent reactions.
BACKGROUND: Exposure of blood to artificial surfaces, as in cardiopulmonary bypass, induces an inflammatory response involving complement, leukocyte and platelet activation. To elucidate the specific role of complement in this process, studies were performed on blood circulated in polyvinyl chloride tubing in the absence and presence of complement inhibitors. Parallel experiments were performed with heparin-coated polyvinyl chloride tubing, which is known to prevent complement and cell activation. METHODS: A novel experimental model was used, based on human whole blood anticoagulated with lepirudin. Complement activation products, myeloperoxidase, lactoferrin, and thrombospondin were quantified in enzyme immunoassays. Leukocyte CD11b expression and leukocyte-platelet conjugates were detected by flow cytometry. RESULTS: Increased levels of C3 activation products, alternative pathway convertase, and the terminal SC5b-9 complex, combined with unchanged levels of C1rs-C1-inhibitor complexes and marginal changes in C4 activation demonstrated that complement was activated through the alternative pathway. Granulocyte and monocyte CD11b expression and granulocyte-platelet conjugate formation were efficiently attenuated by blocking either factor D, C3, C5, or C5a receptor. In contrast, monocyte-platelet conjugate formation and release of myeloperoxidase, lactoferrin, and thrombospondin were not reduced by complement inhibition. Heparin-coated polyvinyl chloride tubing efficiently reduced all inflammatory markers studied, except for C1rs-C1-inhibitor complexes, which increased, consistent with the enhancing effect of heparin on C1-inhibitor function. This effect did not, however, reduce fluid-phase classic pathway activation induced by heat-aggregated immunoglobulin G. CONCLUSIONS: Leukocyte and platelet activation in response to artificial materials occur by mechanisms that vary in their dependence on complement. Heparin coating precludes both the complement-dependent and complement-independent reactions.
Authors: You-Qiang Wu; Hongchang Qu; Georgia Sfyroera; Apostolia Tzekou; Brian K Kay; Bo Nilsson; Kristina Nilsson Ekdahl; Daniel Ricklin; John D Lambris Journal: J Immunol Date: 2011-02-21 Impact factor: 5.422
Authors: Kristina N Ekdahl; John D Lambris; Hans Elwing; Daniel Ricklin; Per H Nilsson; Yuji Teramura; Ian A Nicholls; Bo Nilsson Journal: Adv Drug Deliv Rev Date: 2011-07-08 Impact factor: 15.470
Authors: Zhen Bian; Lei Shi; Ya-Lan Guo; Zhiyuan Lv; Cong Tang; Shuo Niu; Alexandra Tremblay; Mahathi Venkataramani; Courtney Culpepper; Limin Li; Zhen Zhou; Ahmed Mansour; Yongliang Zhang; Andrew Gewirtz; Koby Kidder; Ke Zen; Yuan Liu Journal: Proc Natl Acad Sci U S A Date: 2016-08-30 Impact factor: 11.205
Authors: Knut Tore Lappegård; Dorte Christiansen; Anne Pharo; Ebbe Billmann Thorgersen; Bernt Christian Hellerud; Julie Lindstad; Erik Waage Nielsen; Grethe Bergseth; Dag Fadnes; Tore G Abrahamsen; E Arne Høiby; Lone Schejbel; Peter Garred; John D Lambris; Morten Harboe; Tom Eirik Mollnes Journal: Proc Natl Acad Sci U S A Date: 2009-08-26 Impact factor: 11.205
Authors: Adam Z Blatt; Gurpanna Saggu; Koustubh V Kulkarni; Claudio Cortes; Joshua M Thurman; Daniel Ricklin; John D Lambris; Jesus G Valenzuela; Viviana P Ferreira Journal: J Immunol Date: 2016-04-25 Impact factor: 5.422