A mouse model for in vivo tracking of the major dust mite allergen Der p 2 after inhalation.
Inhaled environmental antigens, i.e. allergens, cause allergic symptoms in millions of patients worldwide. As little is known about the fate of an allergen upon inhalation, we addressed this issue for a major dust mite allergen, Der p 2. First, a model for Der p 2-sensitization was established in C57BL/6 J mice, in which sensitized mice mounted a Der p 2-specific IgE-response with eosinophilic lung inflammation after allergen challenge in the airways. In this model, we applied recombinant Der p 2 carrying a novel C-terminal tetrapeptide Sel-tag enabling labelling with the gamma-emitting radionuclide 75Se at a single selenocysteine residue ([75Se]Der p 2). In vivo tracking of intratracheally administered [75Se]Der p 2 using whole-body autoradiography revealed that [75Se]Der p 2-derived radioactivity persisted in the lungs of sensitized mice as long as 48 h. Radioactivity was also detected in kidneys, liver and in enlarged lung-associated lymph nodes. Interestingly, a larger proportion of radioactivity was found in the lungs of sensitized compared with nonsensitized mice 24 h after intratracheal instillation of [75Se]Der p 2. A radioactive protein corresponding to intact Der p 2 could only be detected in the lungs, whereas [75Se]Der p 2-derived radioactivity was recovered in known selenoproteins both in lung and other organs. Hence, using the recently developed Sel-tag method in a mouse model for Der p 2-sensitization, we could track the fate of an inhaled allergen in vivo. Based upon our findings, we conclude that the inflammatory state of the lung influences the rate of metabolism and clearance of Der p 2. Thus, an allergic response to the inhaled allergen may lead to prolonged retention of Der p 2 in the lung.
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institute and University Hospital, Stockholm, Sweden.
Linda
L
Johansson
Linda
L
Svensson
Ulrika
U
Bergström
Gunilla
G
Jacobsson-Ekman
Elias S J
ES
Arnér
Marianne
M
van Hage
Anders
A
Bucht
Guro
G
Gafvelin
D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007962:Leukocytes; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008925:Mites / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000473:pathology; D011852:Radioallergosorbent Test; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D012644:Selenium Radioisotopes
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D012644:Selenium Radioisotopes; D007073:Immunoglobulin E