House dust mite-induced airway changes in hu-SCID mice.
SCID (severe combined immunodeficiency) mice reconstituted with peripheral blood mononuclear cells (PBMC) from Dermatophagoides pteronissynus (Dpt)-sensitive patients and exposed to Dpt aerosol (allergic hu-SCID mice) develop human IgE and pulmonary inflammation. The present study investigated concomitant changes in airway hyperresponsiveness (AHR). No significant difference in baseline airway responsiveness was seen between nonreconstituted SCID mice exposed or not to Dpt aerosol at Day 35. Allergic hu-SCID mice developed AHR (provocative dose of carbachol causing a 50% increase in lung resistance [PD(50) RL] = 96.33 +/- 16.88 microg/kg) compared with nonallergic hu-SCID mice (PD(50) RL = 242.03 +/- 37.84 microg/kg) and nonreconstituted SCID mice (PD(50) RL = 297.60 +/- 45. 60 microg/kg) exposed to Dpt aerosol. An inverse correlation was observed between PD(50) RL (Day 35) and total human IgE at Day 7 (r = -0.58) and Day 15 (r = -0.64). However, no correlation existed between PD(50) RL and human cell number in the lungs of allergic hu-SCID mice. Moreover, despite the absence of eosinophils, the bronchoalveolar lavage fluid (BALF) of allergic hu-SCID mice had more human interleukin-5 (IL-5) (3.28 +/- 0.40 pg/ml, n = 13) than nonallergic hu-SCID mice (< 0.5 pg/ml) which inversely correlated with the PD(50) RL (r = -0.61). No tumor necrosis factor-alpha (TNF-alpha), IL-6, or IL-4 was detected. These observations indicate that humanized allergic hu-SCID mice may develop AHR after exposure to the relevant allergen, suggesting that this model may improve our understanding of AHR, one characteristic feature of allergic asthma.
Duez
C
C
INSERM U416, Institut Pasteur de Lille, Lille, France.
Kips
J
J
Pestel
J
J
Tournoy
K
K
Tonnel
A B
AB
Pauwels
R
R
D000403:Airway Resistance; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D039741:Antigens, Dermatophagoides; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000737:chemistry / Q000166:cytology; D006023:Glycoproteins / Q000009:adverse effects*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008925:Mites; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D015848:Interleukin-5; D007073:Immunoglobulin E; D017493:Leukocyte Common Antigens