Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis

Publication date: Available online 17 July 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Bianca Balbino, Riccardo Sibilano, Philipp Starkl, Thomas Marichal, Nicolas Gaudenzio, Hajime Karasuyama, Pierre Bruhns, Mindy Tsai, Laurent L. Reber, Stephen J. Galli
BackgroundConflicting results have been obtained regarding 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, as various adjuvants might differentially influence the production of particular antibody isotypes.ObjectiveWe developed an 'adjuvant-free' mouse model of ASA and assessed the contributions of components of the 'classical' and 'alternative' pathways in this model.MethodsMice were sensitized intra-peritoneally (i.p.) with ovalbumin at weekly intervals for 6 weeks and challenged i.p. with ovalbumin two weeks later.ResultsWild-type animals developed immediate hypothermia and late-phase intra-peritoneal 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 (PAF) and histamine and were reduced in two 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.ConclusionComponents of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for mast cells and monocytes/macrophages.

Teaser

FcεRI, FcγRIII, mast cells, histamine, and PAF are required for full development of hypothermia and numbers of infiltrating leukocytes in an adjuvant-free ASA model. Monocytes/macrophages also contribute to hypothermia in this model.


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