Sensitization to inhaled ryegrass pollen by collateral priming in a murine model of allergic respiratory disease.
BACKGROUND
Mouse models of asthma suffer from the necessity to prime the animals by injections before respiratory exposure. Our aim was to develop a mouse model that mimics the progression of human allergic disease upon low-dose inhaled allergen exposure.


METHODS
Mice were primed intraperitoneally to ovalbumin (OVA) before they were exposed repeatedly to aerosols of either OVA, ryegrass (Lolium perenne) pollen extract, or both concomitantly. The sensitization to ryegrass pollen proteins was evaluated by measurement of specific serum antibody, by the respiratory response to a challenge with ryegrass pollen extract and by lung cytokine production after challenge.


RESULTS
Inhalation of ryegrass pollen extract alone did not result in sensitization. Sensitization to inhaled ryegrass pollen proteins, however, did occur in mice that had been sensitized to OVA by intraperitoneal injections and were then exposed to inhaled ryegrass pollen extract and OVA simultaneously. T and B cell priming was ascertained by ryegrass pollen-specific IgG1 and IgE antibody production and by induction of airway inflammation and of Th2 cytokine mRNA transcripts in the lungs upon airway challenge with ryegrass pollen extract. A progressive spread of the IgE/IgG1 response to different ryegrass pollen proteins could be visualized in immunoblots by comparing antibody patterns at day 56 and 86.


CONCLUSIONS
Low-dose inhalatory allergen exposure results in sensitization when airways are exposed at the same time to another allergen to which the animals are already sensitized. This model can help to unravel the mechanisms that underlie the development and progression of respiratory allergic diseases.
Cadot
Pascal
P
Catholic University of Leuven, Belgium. pascal.cadot@xpepharma.com
Meyts
Isabelle
I
Vanoirbeek
Jeroen A J
JA
Vanaudenaerde
Bart
B
Bullens
Dominique M A
DM
Ceuppens
Jan L
JL
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000473:pathology; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008129:Lolium / Q000276:immunology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010936:Plant Extracts / Q000008:administration & dosage / Q000276:immunology; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology; D011058:Pollen / Q000737:chemistry / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D052179:Antigens, Plant; D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D010936:Plant Extracts; D010940:Plant Proteins; D016210:Methacholine Chloride; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin