title: Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis.
abstract: Conflicting results have been obtained regarding the roles of Fc receptors and effector cells in models of active systemic anaphylaxis (ASA). In part, this might reflect the choice of adjuvant used during sensitization because various adjuvants might differentially influence the production of particular antibody isotypes.
  
  
  
  We developed an "adjuvant-free" mouse model of ASA and assessed the contributions of components of the "classical" and "alternative" pathways in this model.
  
  
  
  Mice were sensitized intraperitoneally with ovalbumin at weekly intervals for 6 weeks and challenged intraperitoneally with ovalbumin 2 weeks later.
  
  
  
  Wild-type animals had immediate hypothermia and late-phase intraperitoneal inflammation in this model. These features were reduced in mice lacking the IgE receptor FcεRI, the IgG receptor FcγRIII or the common γ-chain FcRγ. FcγRIV blockade resulted in a partial reduction of inflammation without any effect on hypothermia. Depletion of monocytes/macrophages with clodronate liposomes significantly reduced the hypothermia response. By contrast, depletion of neutrophils or basophils had no significant effects in this ASA model. Both the hypothermia and inflammation were dependent on platelet-activating factor and histamine and were reduced in 2 types of mast cell (MC)-deficient mice. Finally, engraftment of MC-deficient mice with bone marrow-derived cultured MCs significantly exacerbated the hypothermia response and restored inflammation to levels similar to those observed in wild-type mice.
  
  
  
  Components of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for MCs and monocytes/macrophages.
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM, U1222, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Bianca
authors.initials: B
authors.lastname: Balbino
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sibilano
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Philipp
authors.initials: P
authors.lastname: Starkl
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gaudenzio
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM, U1222, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Mindy
authors.initials: M
authors.lastname: Tsai
authors.affiliation: Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM, U1222, Paris, France; Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif. Electronic address: laurent.reber@pasteur.fr.
authors.forename: Laurent L
authors.initials: LL
authors.lastname: Reber
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, Calif. Electronic address: sgalli@stanford.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000276:Adjuvants, Immunologic; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004195:Disease Models, Animal; D006801:Humans; D007035:Hypothermia / Q000276:immunology*; D007114:Immunization; D007962:Leukocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; C579617:FcepsilonRIalpha protein, mouse; C485700:Fcgr3 protein, mouse; C522404:Fcgr4 protein, mouse; D017455:Receptors, IgE; D017452:Receptors, IgG
keywords: Fc receptors; Rodents; allergy; anaphylaxis; antibodies; inflammation; mast cells/basophils; monocytes/macrophages; mouse model; neutrophils