Pathways of anaphylaxis in the mouse.
BACKGROUND
Although anaphylaxis is classically mediated by IgE, FcepsilonRI, mast cells, and histamine, several rodent studies suggest that an alternative pathway involving IgG, FcgammaRIII, macrophages and platelets, and platelet-activating factor (PAF) may be more important in the anaphylactic response to antigen challenge.


OBJECTIVE
We sought to determine the relative roles of the classical and alternative pathways of anaphylaxis in a mouse model characterized by mastocytosis and a high level of antigen-specific IgE antibody.


METHODS
Wild-type, IgE-deficient, FcepsilonRI-deficient, and mast cell-deficient mice were immunized with goat anti-mouse IgD antibody, which induces mastocytosis and a large IgE and IgG anti-goat IgG response, and then challenged 14 days later with antigen (goat IgG) or rat anti-mouse IgE mAb. Specific vasoactive mediators, cell types, Ig isotypes, or Ig receptors were blocked or eliminated before challenge in some experiments. The severity of anaphylaxis was gauged by changes in body temperature, physical activity, and mortality.


RESULTS
Equal doses of antigen or anti-IgE mAb induced similar anaphylactic responses. Anti-IgE mAb-induced anaphylaxis was FcepsilonRI and mast cell dependent and mediated predominantly by histamine. In contrast, neither mast cells nor platelets appeared important for antigen-induced anaphylaxis, which was FcgammaRIII and macrophage dependent and mediated predominantly by PAF.


CONCLUSIONS
Antigen-induced anaphylaxis in the mouse proceeds primarily through the IgG, FcgammaRIII, macrophage, and PAF pathway, even in an experimental model that is characterized by strong mast cell and IgE responses. The presence of FcgammaRIII on human macrophages makes it possible that the IgG, FcgammaRIII, macrophage, and PAF pathway also contributes to human anaphylaxis.
Strait
Richard T
RT
Division of Emergency Medicine, Children's Hospital Medical Center, Cincinnati, USA.
Morris
Suzanne C
SC
Yang
Mingyan
M
Qu
Xiao-Wu
XW
Finkelman
Fred D
FD
D000707:Anaphylaxis / Q000209:etiology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001792:Blood Platelets / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D005260:Female; D007074:Immunoglobulin G / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010972:Platelet Activating Factor / Q000502:physiology; D017455:Receptors, IgE / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology; D012701:Serotonin / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000941:Antigens; D007074:Immunoglobulin G; D010972:Platelet Activating Factor; D017455:Receptors, IgE; D017452:Receptors, IgG; C026408:anti-IgE antibodies; D012701:Serotonin; D003165:Complement System Proteins