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Am. J. Respir. Crit. Care Med., Volume 161, Number 1, January 2000, 200-206

House Dust Mite-induced Airway Changes in hu-SCID Mice

CATHERINE DUEZ, JOHAN KIPS, JOËL PESTEL, KURT TOURNOY, ANDRÉ-BERNARD TONNEL, and ROMAIN PAUWELS

INSERM U416, Institut Pasteur de Lille, Lille, France; Cliniques des Maladies Respiratoires, CHRU, Lille, France; and Department of Respiratory Disease, University Hospital Gent, Gent, Belgium

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 [PD50 RL] = 96.33 ± 16.88 µg/kg) compared with nonallergic hu-SCID mice (PD50 RL = 242.03 ± 37.84 µg/kg) and nonreconstituted SCID mice (PD50 RL = 297.60 ± 45.60 µg/kg) exposed to Dpt aerosol. An inverse correlation was observed between PD50 RL (Day 35) and total human IgE at Day 7 (r = -0.58) and Day 15 (r = -0.64). However, no correlation existed between PD50 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 PD50 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, Kips J, Pestel J, Tournoy K, Tonnel A-B, Pauwels R. House dust mite-induced airway changes in hu-SCID mice.




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