A study on the airway remodeling in an asthma model using bikunin knock out mice.

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【Aims】 It is possible that hyarulonan is related to the pathogenesis of asthma by affecting mucus production and ciliary beat in airways. In order to directly prove this hypothesis, we investigated airway responsiveness using bikunin knock out (BXO) mice, which is essential for the transfer reaction of serum-derived hyarulonan associated protein (SHAP).【Methods】 We made BXO mice form DBA1 or BALBC strain. We sensitized mice with intraperitoneal injection of ovalbumin (OVA) mixed with aluminum hydrochloride at days 1 and 15. Airway sensitization was done by inhalation of 1% OVA solution for 2 weeks from day 23 to 36, or for 4 weeks from day 23 to 50. Nonspecific airway responses to methacholine and OVA-specific airway responses were measured by body pletysmograph (Buxco) at day 22 or day 37, and at day 26 or day 37, respectively.【Results】 There was no significant difference in immediate airway responses to OVA between wild and BXO mice three days or ten days after the initiation of sensitization with OVA inhalation. Similar results were obtained for nonspecific airway responses to methacholine inhalation. No significant difference was observed for serum levels of OVA-specific IgE and IgG, and for bronchoalveolar lavage findings between the two strains. No significant difference was found for airway responses even in 4-week sensitization mice between the two strains ; however, serum levels of OVA-specific IgG were significantly increased in BXO mice.【Discussion】 We have failed to find distinct differences in airway responses in the current study. We should evaluate airway responses also by measuring intratracheal pressure not by body pletysmography. We should also verify the existence of altered content of HA or SHAP as a prerequisite of pathological changes in airways.