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)-se nsitive patients and exposed to Dpt aerosol (allergic hu-SCID mice) develop human IgE and pulmonary inflammation. The present study investigated conco mitant changes in airway hyperresponsiveness (AHR). No significant differen ce in baseline airway responsiveness was seen between nonreconstituted SCID mice exposed or not to Dpt aerosol at Day 35. Allergic hu-SCID mice develo ped AHR (provocative dose of carbachol causing a 50% increase in lung resis tance [PD50 RL] = 96.33 +/- 16.88 mu g/kg) compared with nonallergic hu-SCI D mice (PD50 RL = 242.03 +/- 37.84 mu g/kg) and nonreconstituted SCID mice (PD50 RL = 297.60 +/- 45.60 mu g/kg) exposed to Dpt aerosol. An inverse cor relation was observed between PDS, Rr (Day 35) and total human IgE at Day 7 (r = -0.58) and Day 15 (r = -0.64). However, no correlation existed betwee n PD50 RL and human cell number in the lungs of allergic hu-SCID mice. More over, despite the absence of eosinophils, the bronchoalveolar ravage 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 in versely correlated with the PD50 RL (r = -0.61). No tumor necrosis factor-a lpha (TNF-alpha), IL-6, or IL-4 was detected. These observations indicate t hat humanized allergic hu-SCID mice may develop AHR after exposure to the r elevant allergen, suggesting that this model may improve our understanding of AHR, one characteristic feature of allergic asthma.