Artificial Surface-Induced Inflammation Relies on Complement Factor 5: Proof From a Deficient Person

• Published in: The Annals of thoracic surgery Vol. 91; no. 2; pp. 527 - 533
• Main Authors: Bergseth, Grethe, Lambris, John D., Mollnes, Tom Eirik, Lappegård, Knut Tore
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2011; Elsevier
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biocompatible Materials - adverse effects; Biological and medical sciences; Cardiology. Vascular system; Cardiothoracic Surgery; Cell Degranulation - immunology; Chemokines - blood; Complement Activation; Complement C5 - deficiency; Complement C5 - immunology; Cytokines - blood; Environmental Exposure - adverse effects; Flow Cytometry; Humans; In Vitro Techniques; Inflammation - blood; Inflammation - immunology; Medical sciences; Neutrophils - immunology; Pneumology; Surgery; PBS; 25; IL; VEGF; EDTA; C5a; INF-γ; C3; C5; TCC; C9; C5aRA; MCP; C5aR; PVC; PDGF-BB; complement factor 5; complement factor 3; complement factor 5a receptor; platelet-derived growth factor-BB; ethylenediaminetetraacetic acid; interleukin; monocyte chemoattractant protein; complement factor 5a receptor antagonist; interferon gamma; complement factor 5a; complement factor 9; phosphate buffered saline; vascular endothelial growth factor; polyvinyl chloride; terminal complement complex; Anesthesia; Complement; Inflammation; Circulatory system; Cardiology; Surface
• ISSN: 0003-4975; 1552-6259; 1552-6259
• DOI: 10.1016/j.athoracsur.2010.10.084

Exposing blood to artificial surfaces results in an inflammatory response, including complement activation and cytokine release. The aim of this investigation was to study complement-dependency and independency in artificial surface-induced inflammation in human whole blood from a patient with a genetic deficiency of complement factor 5 (C5). Whole blood from a C5-deficient patient, C5 protein reconstituted blood, and blood from a control subject was used. The complement inhibitor compstatin (C3 inhibitor) and a C5a receptor antagonist were used to block complement. Blood was circulated in closed loops of polyvinyl chloride tubing. Leukocyte CD11b expression and release of granule enzymes (myeloperoxidase, elastase, lactoferrin), cytokines (interleukins, chemokines, and growth factors; n = 27) as well as complement activation were measured after incubation. In C5-deficient blood, there was no formation of the terminal complement complex, as opposed to reconstituted or control blood. Release of granule enzymes was partly dependent on C3, revealed by a compstatin-dependent effect in C5-deficient blood, and partly C5a-dependent as evident from the reconstitution and control blood. The chemokines interleukin-8 and monocyte chemoattractant protein-1 were also highly complement dependent, the effect being C5a-mediated, whereas platelet-derived and vascular endothelial growth factors were partly complement dependent. Interferon-γ increased in a complement-independent manner, whereas the rest of the cytokines did not respond to the surface. Leukocyte expression of CD11b was only marginally increased in deficient blood exposed to the surface, whereas reconstitution induced a considerable, C5a-dependent increase, comparable with that of the control. The polyvinyl chloride surface induced a defined inflammatory response, which largely depended on C5.