Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 139, Issue 2, Pages 584-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.05.047
Keywords
Rodents; mouse model; mast cells/basophils; monocytes/macrophages neutrophils; antibodies; Fc receptors; allergy; inflammation; anaphylaxis
Categories
Funding
- Pasteur-Paris University (PPU) International PhD Program
- Lucile Packard Foundation for Children's Health
- Stanford National Institutes of Health (NIH)/NCRR CTSA [UL1 RR025744]
- Max Kade Fellowship of the Max Kade Foundation
- Schroedinger Fellowship of the Austrian Science Fund (FWF) [J3399-B21]
- European Commission Marie Sklodowska-Curie Individual Fellowship [H2020-MSCA-IF-2014655153]
- Marie Curie International Outgoing Fellowship for Career Development [299954]
- Charge de recherches'' fellowship of the Belgian National Fund for Scientific Research (F.R. S-FNRS)
- French Fondation pour la Recherche Medicale FRM
- European Research Council (ERC)-Seventh Framework Program [ERC-2013-CoG 616050]
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Institut Pasteur
- Stanford Pediatric Research Fund of the Lucile Packard Foundation for Children's Health
- Stanford CTSA (National Institutes of Health) [UL1 RR025744]
- NIH [K99AI110645, AI023990, CA072074, AI070813, AR067145, U19 AI104209, NS 080062]
- European Commission Marie SklodowskaCurie Individual Fellowship [H2020-MSCA-IF-2014 656086]
- French Institut National de la Sante et de la Recherche Medicale'' (INSERM)
- Tobacco-Related Disease Research Program at the University of California
- Department of Pathology, Stanford University School of Medicine
- Austrian Academy of Sciences
- Grants-in-Aid for Scientific Research [15H05786] Funding Source: KAKEN
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Background: 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. Objective: We developed an adjuvant-free'' mouse model of ASA and assessed the contributions of components of the classical'' and alternative'' pathways in this model. Methods: Mice were sensitized intraperitoneally with ovalbumin at weekly intervals for 6 weeks and challenged intraperitoneally with ovalbumin 2 weeks later. Results: Wild-type animals had immediate hypothermia and late-phase intraperitoneal inflammation in this model. These features were reduced in mice lacking the IgE receptor Fc epsilon RI, the IgG receptor Fc gamma RIII or the common gamma-chain FcR gamma. Fc gamma RIV 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. Conclusion: Components of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for MCs and monocytes/macrophages.
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