title: Capability of Neutrophils to Form NETs Is Not Directly Influenced by a CMA-Targeting Peptide.
abstract: During inflammatory reaction, neutrophils exhibit numerous cellular and immunological functions, notably the formation of neutrophil extracellular traps (NETs) and autophagy. NETs are composed of decondensed chromatin fibers coated with various antimicrobial molecules derived from neutrophil granules. NETs participate in antimicrobial defense and can also display detrimental roles and notably trigger some of the immune features of systemic lupus erythematosus (SLE) and other autoimmune diseases. Autophagy is a complex and finely regulated mechanism involved in the cell survival/death balance that may be connected to NET formation. To shed some light on the connection between autophagy and NET formation, we designed a number of experiments in human neutrophils and both in normal and lupus-prone MRL/lpr mice to determine whether the synthetic peptide P140, which is capable of selectively modulating chaperone-mediated autophagy (CMA) in lymphocytes, could alter NET formation. P140/Lupuzor™ is currently being evaluated in phase III clinical trials involving SLE patients. Overall ourin vitroandin vivostudies established that P140 does not influence NET formation, cytokine/chemokine production, or CMA in neutrophils. Thus, the beneficial effect of P140/Lupuzor™ in SLE is apparently not directly related to modulation of neutrophil function.
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Maueröder
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire , Strasbourg , France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schall
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire , Strasbourg , France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Meyer
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany.
authors.forename: Aparna
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire , Strasbourg , France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Garnier
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kienhöfer
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen , Erlangen , Germany.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Hoffmann
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France; University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
keywords: NET formation; P140/Lupuzor; autophagy; murine models of lupus; neutrophils; systemic lupus erythematosus