Role of mast cell degranulation in the neural correlates of the immediate allergic reaction in a murine model of asthma.
Experimental airway allergy in mice leads to increased activity in specific hypothalamic and amygdaloid nuclei, and behavioral changes. The experiments described here were designed to determine the role of anaphylactic antibodies, mast cell degranulation, and lung inflammation in the neural and behavioral correlates of an experimental murine asthma-like response. Animals were sensitized intraperitoneally with ovalbumin adsorbed to alum, and challenged by intranasal ovalbumin instillation or aerosol. To induce immunological tolerance, animals were fed ovalbumin in the drinking water for 5 consecutive days, along with primary sensitization. Depletion of IgE was also accomplished with a non-anaphylactic anti-IgE antibody. Mast cell degranulation was inhibited by cromolyn. In addition to BALB/c animals, C3H/HeJ mice were used for their relative resistance to lung allergic inflammation. We confirmed that ovalbumin challenge in allergic mice leads to increased activity in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and avoidance behavior towards an allergen-associated compartment. Moreover, these responses were precluded by oral tolerance or anti-IgE treatment, even in the presence of IgG1. Cromolyn abrogates both responses in the presence of anaphylactic antibodies. Finally, although sensitized C3H/HeJ mice did not develop airway inflammation, they exhibited brain and behavioral changes similar to BALB/c animals. The repercussions of murine allergic asthma on brain and behavior are IgE-dependent, mediated by mast cell degranulation, and do not require a pulmonary inflammatory infiltrate, suggesting that the early phase of this immediate allergic response suffices for the brain activation associated with avoidance behavior towards exposure to the allergen.
Costa-Pinto
Frederico Azevedo
FA
Department of Pathology, School of Veterinary Medicine, University of Sao Paulo, Brazil. fpinto@usp.br
Basso
Alexandre Salgado
AS
Russo
Momtchilo
M
D000679:Amygdala / Q000276:immunology / Q000502:physiology*; D000704:Analysis of Variance; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D015550:Cell Degranulation / Q000276:immunology*; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015213:Neuroimmunomodulation / Q000276:immunology / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D010286:Paraventricular Hypothalamic Nucleus / Q000276:immunology / Q000502:physiology*; D013045:Species Specificity; D018709:Statistics, Nonparametric
D007073:Immunoglobulin E; D010047:Ovalbumin