Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice.
gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcstraightepsilonRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.
Daheshia
M
M
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Friend
D S
DS
Grusby
M J
MJ
Austen
K F
KF
Katz
H R
HR
D000707:Anaphylaxis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D004487:Edema / Q000209:etiology / Q000276:immunology / Q000473:pathology; D005260:Female; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic
D000954:Antigens, Surface; C489447:Gp49a protein, mouse; C489448:Lilrb4 protein, mouse; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D010047:Ovalbumin