Mechanisms of AllergyPathways of anaphylaxis in the mouse☆,☆☆
Section snippets
Mice
Female BALB/c mice were purchased from NCI (Frederick, Md). IgE-deficient mice (FVBN background, a gift from P. Leder, Cambridge, Mass)13 and FcϵRIα-deficient mice (BALB/c background, a gift from J.-P. Kinet, Cambridge, Mass)14 were bred in our animal facility along with the appropriate wild-type control animals. W/Wv (mast cell–deficient) mice and litter mate control mice15 were purchased from Jackson Labs (Bar Harbor, Me). All mice were age and sex matched within experiments and were used at
Anti-igE mAb– and antigen-induced anaphylaxis have similar severities, kinetics, and sensitivities
Injection of mice with GaMD stimulates large IgG and IgE anti-GIgG antibody responses.24 Challenge of GaMD-primed mice with either antigen (GIgG) or anti-IgE mAb intravenously 14 days after priming induces anaphylaxis. The severity, kinetics, and dose-response characteristics of anaphylaxis induced by injection of antigen or anti-IgE mAb were compared by evaluating decreases in mouse activity and rectal temperature for 2 hours after challenge (Fig 1, left and middle panels).
Discussion
Although anaphylaxis classically involves IgE, mast cells, and FcϵRI, recent studies have demonstrated that none of these is required for the development of antigen-induced shock in previously immunized rodents. These studies also provided evidence for an alternative pathway in which IgG, non–mast cells (macrophages, granulocytes, and platelets), and FcγRIII are important.3, 4, 5, 28, 29, 34, 35, 36, 37, 38 We have examined the potential importance of each of these elements to determine whether
Acknowledgements
We thank Edward Giannini for assistance with statistical analysis and Tatyana Orekhova, Kristi Smiley, Brian Meister, and Sasha Simms for technical assistance.
References (48)
FcεRI-expressing antigen-presenting cells: new players in the atopic game
Immunol Today
(1997)- et al.
Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor α chain gene
Cell
(1993) - et al.
Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation
Blood
(1978) - et al.
A novel function for transforming growth factor-β1: upregulation of the expression and the IgE-Independent extracellular release of a mucosa mast cell granule-specific β-chymase, mouse mast cell protease-1
Blood
(1999) - et al.
A novel anti-platelet monoclonal antibody induces mouse platelet aggregation through an Fc receptor-independent mechanism
Biochem Biophys Res Commun
(1998) - et al.
Anaphylaxis and food allergy
Clin Rev Allergy Immunol
(1999) - et al.
Fatal and near-fatal anaphylactic reactions to food in children and adolescents
N Engl J Med
(1992) - et al.
Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and FcγRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-depend-ent passive anaphylaxis
J Clin Invest
(1997) - et al.
Absence of FcεRIα chain results in upregulation of FcγRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between FcεRI and FcγRIII for limiting amounts of FcR β and γ chains
J Clin Invest
(1997) - et al.
Inhibition of anaphylactic shock by gadolinium chloride-induced Kupffer cell blockade
Agents Actions
(1994)
Horse gammaglobulin-induced thrombocytopenia in anaphylaxis involving sequestration and activation of platelets
Clin Exp Allergy
Human HMC-1 mast cells exclusively express the FcγRII subtype of IgG receptor
Arch Dermatol Res
Expression of functional high affinity immunoglobulin E receptors (FcεRI) on monocytes of atopic individuals
J Exp Med
Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody
J Immunol
Polyclonal activation of the murine immune system by a goat antibody to mouse IgD. IX. Induction of a polyclonal IgE response
J Immunol
IgD-secreting murine plasmacytomas: identification and partial characterization of two IgD myeloma proteins
J Immunol
Active anaphylaxis in IgE-deficient mice
Nature
Inhibition of IgE binding to mast cells and basophils by monoclonal antibodies to murine IgE
Eur J Immunol
Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors
J Exp Med
An eosinophil-dependent mechanism for the antitumor effect of interleukin-4
Science
Modulation of immunoglobulin (Ig)E-mediated systemic anaphylaxis by low-affinity Fc receptors for IgG
J Exp Med
Gadolinium induces macrophage apoptosis
J Leukoc Biol
Neuraminidase-induced thrombocytopenia in mice: effects on thrombopoiesis
J Cell Physiol
Cross-linking of membrane immunoglobulin D, in the absence of T cell help, kills mature B cells in vivo
J Exp Med
Cited by (0)
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Supported by a Merit Award (to FDF) from the Veteran's Administration and National Institutes of Health grants RO1 AI45766, KO8 AI50006, and P60-AR-44059.
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Reprint requests: Fred D. Finkelman, MD, Research Service (151), Cincinnati VAMC, 3200 Vine St, Cincinnati, OH 45220.