title: Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2.
abstract: All 3 activation pathways of complement-the classic pathway (CP), the alternative pathway, and the lectin pathway (LP)- converge into a common central event: the cleavage and activation of the abundant third complement component, C3,viaformation of C3-activating enzymes (C3 convertases). The fourth complement component, C4, and the second component, C2, are indispensable constituents of the C3 convertase complex, C4bC2a, which is formed by both the CP and the LP. Whereas in the absence of C4, CP can no longer activate C3, LP retains a residual but physiologically critical capacity to convert native C3 into its activation fragments, C3a and C3b. This residual C4 and/or C2 bypass route is dependent on LP-specific mannan-binding lectin-associated serine protease-2. By using various serum sources with defined complement deficiencies, we demonstrate that, under physiologic conditions LP-specific C4 and/or C2 bypass activation of C3 is mediated by direct cleavage of native C3 by mannan-binding lectin-associated serine protease-2 bound to LP-activation complexes captured on ligand-coated surfaces.-Yaseen, S., Demopulos, G., Dudler, T., Yabuki, M., Wood, C. L., Cummings, W. J., Tjoelker, L. W., Fujita, T., Sacks, S., Garred, P., Andrew, P., Sim, R. B., Lachmann, P. J., Wallis, R., Lynch, N., Schwaeble, W. J. Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2.
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom.|Omeros Corporation, Seattle, Washington, USA.|Department of Biology, University of Mosul, Mosul, Iraq.
authors.forename: Sadam
authors.initials: S
authors.lastname: Yaseen
authors.affiliation: Omeros Corporation, Seattle, Washington, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Demopulos
authors.affiliation: Omeros Corporation, Seattle, Washington, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dudler
authors.affiliation: Omeros Corporation, Seattle, Washington, USA.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Yabuki
authors.affiliation: Omeros Corporation, Seattle, Washington, USA.
authors.forename: Christi L
authors.initials: CL
authors.lastname: Wood
authors.affiliation: Omeros Corporation, Seattle, Washington, USA.
authors.forename: W Jason
authors.initials: WJ
authors.lastname: Cummings
authors.affiliation: Omeros Corporation, Seattle, Washington, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Tjoelker
authors.affiliation: Fukushima Prefectural General Hygiene Institute, Fukushima Medical University, Fukushima City, Japan.
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Medical Research Council (MRC) Centre for Transplantation, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Sacks
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Andrew
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lachmann
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Russell
authors.initials: R
authors.lastname: Wallis
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lynch
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom; ws5@le.ac.uk.
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schwaeble
mesh_terms: D003167:Complement Activation / Q000502:physiology*; D003175:Complement C2 / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*
chemical_list: C038245:C3 protein, human; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: activation bypass; innate immunity; opsonization; post-ischemic inflammation