Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice.
Wide differences among inbred mouse strains in susceptibility to develop components of asthmalike pulmonary changes would provide insights into the nature of the relationships among those components and set the stage for genetic approaches to their etiology. We therefore examined pulmonary pathophysiological and serum immunoglobulin (Ig)E responses in mice of 12 inbred strains sensitized intraperitoneally with ovalbumin (OVA) and repeatedly exposed to aerosolized OVA. One day after the last OVA exposure the intravenous methacholine (MCh) dose required to reduce lung conductance by 50% (ED(50)GL) in OVA-sensitized and exposed mice was reduced by 0 to 2.7-fold, compared with sham-sensitized mice, depending on the strain. In OVA-sensitized mice, bronchoalveolar lavage (BAL) eosinophils comprised from 3.3 +/- 3.1 (SD) to 91.2 +/- 5.0% of BAL cells and eosinophilic pulmonary inflammation varied from being nondetectable to widespread and severe. OVA-specific IgE concentrations ranged from less than 3 ng/ml to 455 ng/ml in different strains. Shifts in responsiveness correlated significantly with pulmonary eosinophilia among strains (r > 0.70, p < 0.001) but not with antigen-specific IgE levels (r = 0.55, p = 0.056). These results demonstrate that allergen- induced enhancement of cholinergic responsiveness, pulmonary eosinophil influx, and elevations of serum antigen-specific IgE levels are each genetically determined and are not always associated.
Brewer
J P
JP
Perlmutter Laboratory, Department of Pediatrics, Pulmonary Division, Children's Hospital, Boston, MA 02115, USA.
Kisselgof
A B
AB
Martin
T R
TR
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D020022:Genetic Predisposition to Disease; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood*; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology
D000941:Antigens; D007073:Immunoglobulin E; D010047:Ovalbumin