title: Phospholipid scramblase 1 amplifies anaphylactic reactions in vivo.
abstract: Mast cells are critical actors of hypersensitivity type I (allergic) reactions by the release of vasoactive and proinflammatory mediators following their activation by aggregation of the high-affinity receptor for immunoglobulin E (FcεRI). We have previously identified Phospholipid Scramblase 1 (PLSCR1) as a new molecular intermediate of FcεRI signaling that amplifies degranulation of the rat mast cell line RBL-2H3. Here we characterized primary mast cells from Plscr1-/- mice. The absence of PLSCR1 expression did not impact mast cell differentiation as evidenced by unaltered FcεRI expression, general morphology, amount of histamine stored and expression of FcεRI signal effector molecules. No detectable mast cell deficiency was observed in Plscr1-/- adult mice. In dose-response and time-course experiments, primary cultures of mast cells (bone marrow-derived mast cells and peritoneal cell-derived mast cells) generated from Plscr1-/- mice exhibited a reduced release of β-hexosaminidase upon FcεRI engagement as compared to their wild-type counterparts. In vivo, Plscr1-/- mice were protected in a model of passive systemic anaphylaxis when compared to wild-type mice, which was consistent with an observed decrease in the amounts of histamine released in the serum of Plscr1-/- mice during the reaction. Therefore, PLSCR1 aggravates anaphylactic reactions by increasing FcεRI-dependent mast cell degranulation. PLSCR1 could be a new therapeutic target in allergy.
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Asma
authors.initials: A
authors.lastname: Kassas-Guediri
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Coudrat
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Pacreau
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Launay
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Blank
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charles
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France.|University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benhamou
mesh_terms: D000707:Anaphylaxis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015550:Cell Degranulation; D002454:Cell Differentiation; D002478:Cells, Cultured; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism
chemical_list: D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse; D017455:Receptors, IgE; D007073:Immunoglobulin E; D006632:Histamine