Immunoglobulin E-dependent active fatal anaphylaxis in mast cell-deficient mice.
Mast cells have long been believed to be the central effector cells in the development of immunoglobulin (Ig)E-dependent anaphylaxis. In this study, we investigated the role of mast cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell-deficient WBB6F1- W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/Wv mice. Administration of monoclonal anti-IL-4 antibody completely prevented the fatal reactions, and the effect of anti-IL-4 was associated with its suppressive activity on Pen V-specific serum levels of IgE, but not IgG. The platelet-activating factor (PAF) antagonist, BN 50739, completely prevented the fatal reactions in both strains of mice. Our kinetic study revealed, in contrast to no elevation of plasma histamine level in W/Wv mice, high levels of PAF in the circulation after challenge in both +/+ and W/Wv mice, albeit to a lesser degree in the latter case. These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis.
Choi
I H
IH
Department of Immunology and Institute for Medical Science, Chonbuk National University Medical School, Chonju, Chonbuk, 561-182, Republic of Korea.
Shin
Y M
YM
Park
J S
JS
Lee
M S
MS
Han
E H
EH
Chai
O H
OH
Im
S Y
SY
Ha
T Y
TY
Lee
H K
HK
D000707:Anaphylaxis / Q000209:etiology* / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D005260:Female; D006241:Haptens; D006632:Histamine / Q000097:blood; D007073:Immunoglobulin E / Q000378:metabolism*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010404:Penicillin V / Q000276:immunology / Q000633:toxicity; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D014230:Triazoles / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001381:Azepines; D006241:Haptens; D010972:Platelet Activating Factor; D014230:Triazoles; C064509:BN 50739; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; D010404:Penicillin V