Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene.
Mast cells and basophils, which are activated by immunoglobulin E (IgE) and allergen, play a prominent role in anaphylaxis. However, they express at least three types of IgE receptor, including the high affinity IgE receptor (Fc epsilon RI). The relative contribution of these IgE receptors, and possibly other receptors such as Fc epsilon RII/CD23 and Mac-2, to the genesis of in vivo anaphylaxis is still unclear. To address this question, we have generated Fc epsilon RI-deficient mice. These mice appear normal and express a normal number of mast cells, but they are resistant to cutaneous and systemic anaphylaxis. These data demonstrate that Fc epsilon RI is necessary for the initiation of IgE-dependent anaphylactic reactions. Therefore, interfering with its function should be an effective means of treating allergy, regardless of the allergen specificity.
Dombrowicz
D
D
Molecular Allergy and Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852.
Flamand
V
V
Brigman
K K
KK
Koller
B H
BH
Kinet
J P
JP
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D017455:Receptors, IgE / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D017931:DNA Primers; D017455:Receptors, IgE; D017452:Receptors, IgG; D012701:Serotonin