title: Lactoferrin Is an Allosteric Enhancer of the Proteolytic Activity of Cathepsin G.
abstract: Protease-mediated degradation of proteins is critical in a plethora of physiological processes. Neutrophils secrete serine proteases including cathepsin G (CatG), neutrophile elastase (NE), and proteinase 3 (PR3) together with lactoferrin (LF) as a first cellular immune response against pathogens. Here, we demonstrate that LF increases the catalytic activity of CatG at physiological concentration, with its highest enhancing capacity under acidic (pH 5.0) conditions, and broadens the substrate selectivity of CatG. On a functional level, the enzymatic activity of CatG was increased in the presence of LF in granulocyte-derived supernatant. Furthermore, LF enhanced CatG-induced activation of platelets as determined by cell surface expression of CD62P. Consequently, LF-mediated enhancement of CatG activity might promote innate immunity during acute inflammation.
authors.affiliation: Department of Neurosurgery, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Eipper
authors.affiliation: Department of Neurosurgery, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Steiner
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
authors.affiliation: Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Sienczyk
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Palesch
authors.affiliation: Department of Neurosurgery, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Marc-Eric
authors.initials: ME
authors.lastname: Halatsch
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Zaczynska
authors.affiliation: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Heim
authors.affiliation: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Hartmann
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Zimecki
authors.affiliation: Department of Neurosurgery, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Christian Rainer
authors.initials: CR
authors.lastname: Wirtz
authors.affiliation: Department of Neurosurgery, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Burster
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D055162:Biocatalysis / Q000187:drug effects; D056649:Cathepsin G / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007113:Immunity, Innate / Q000187:drug effects*; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology; D007781:Lactoferrin / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D059748:Proteolysis / Q000187:drug effects; D013379:Substrate Specificity
chemical_list: D017077:Culture Media, Conditioned; C490098:LTF protein, human; D007781:Lactoferrin; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase