title: Curvature of synthetic and natural surfaces is an important target feature in classical pathway complement activation.
abstract: The binding of Abs to microbial surfaces followed by complement activation constitutes an important line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potently on dextran-coated particles having a diameter around 250 nm, whereas larger (600 nm) particles were less potent activators. This selectivity regarding particle dimension was also found for complement activation by colloidal substances of microbial origin. Peptidoglycan (PGN) is the major chemical component in the cell wall of Gram-positive bacteria. Fragments of purified PGN with sizes of approximately 100 nm promoted complement activation effectively through the classical pathway. By contrast, larger or smaller fragments of PGN did not activate complement strongly. A careful analysis of PGN fragments released during planctonic growth of Staphylococcus aureus showed that these include curvatures that would permit strong IgM-mediated complement activation, whereas the curvature of intact cells would be less effective for such activation. Consistently, we found that the suspended PGN fragments were strong activators of complement through the classical pathway. We suggest that these fragments act as decoy targets for complement activation, providing protection for S. aureus against the host immune response to infection.
authors.affiliation: Interdisciplinary Nanoscience Center, University of Aarhus, Aarhus, Denmark.
authors.forename: Martin Bjerregård
authors.initials: MB
authors.lastname: Pedersen
authors.forename: Xingfei
authors.initials: X
authors.lastname: Zhou
authors.forename: Esben Kjaer Unmack
authors.initials: EK
authors.lastname: Larsen
authors.forename: Uffe Skov
authors.initials: US
authors.lastname: Sørensen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.forename: Jens Vinge
authors.initials: JV
authors.lastname: Nygaard
authors.forename: Jens Randel
authors.initials: JR
authors.lastname: Nyengaard
authors.forename: Rikke Louise
authors.initials: RL
authors.lastname: Meyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Boesen
authors.forename: Thomas
authors.initials: T
authors.lastname: Vorup-Jensen
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001666:Binding Sites, Antibody; D003176:Complement C3 / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology*; D003911:Dextrans / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010457:Peptidoglycan / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding / Q000276:immunology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology* / Q000648:ultrastructure; D013499:Surface Properties
chemical_list: D000942:Antigens, Bacterial; D003176:Complement C3; D003911:Dextrans; D005290:Ferric Compounds; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010457:Peptidoglycan; C000499:ferric oxide