Monensin inhibits mast cell mediated airway contractions in human and guinea pig asthma models

Liu, JieluKarolinska Inst, Inst Environm Med IMM, Expt Asthma & Allergy Res Unit, Biomed, Solnavagen 9, S-17165 Stockholm, Sweden. (författare)

Asthma is a common respiratory disease associated with airway hyperresponsiveness (AHR), airway inflammation and mast cell (MC) accumulation in the lung. Monensin, an ionophoric antibiotic, has been shown to induce apoptosis of human MCs. The aim of this study was to define the effect of monensin on MC responses, e.g., antigen induced bronchoconstriction, and on asthmatic features in models of allergic asthma. Tracheal segments from house dust mite (HDM) extract sensitized guinea pigs were isolated and exposed to monensin, followed by histological staining to quantify MCs. Both guinea pig tracheal and human bronchi were used for pharmacological studies in tissue bath systems to investigate the monensin effect on tissue viability and antigen induced bronchoconstriction. Further, an HDM-induced guinea pig asthma model was utilized to investigate the effect of monensin on AHR and airway inflammation. Monensin decreased MC number, caused MC death, and blocked the HDM or anti-IgE induced bronchoconstriction in guinea pig and human airways. In the guinea pig asthma model, HDM-induced AHR, airway inflammation and MC hyperplasia could be inhibited by repeated administration of monensin. This study indicates that monensin is an effective tool to reduce MC number and MCs are crucial for the development of asthma-like features.

Nie, MuKarolinska Inst, Inst Environm Med IMM, Expt Asthma & Allergy Res Unit, Biomed, Solnavagen 9, S-17165 Stockholm, Sweden. (författare)
Dong, CaijuanKarolinska Inst, Inst Environm Med IMM, Expt Asthma & Allergy Res Unit, Biomed, Solnavagen 9, S-17165 Stockholm, Sweden. (författare)
Säfholm, JesperKarolinska Institutet (författare)
Pejler, GunnarUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)gupej227 (författare)
Nilsson, GunnarKarolinska Institutet,Uppsala universitet,Hematologi,Karolinska Inst, Dept Med, Div Immunol & Allergy, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.(Swepub:uu)gunnarns (författare)
Adner, MikaelKarolinska Institutet (författare)
Karolinska InstitutetKarolinska Inst, Inst Environm Med IMM, Expt Asthma & Allergy Res Unit, Biomed, Solnavagen 9, S-17165 Stockholm, Sweden. (creator_code:org_t)

Av författaren/redakt...: Liu, Jielu; Nie, Mu; Dong, Caijuan; Säfholm, Jesper; Pejler, Gunnar; Nilsson, Gunnar; visa fler...; Adner, Mikael; visa färre...

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