Dissociation of airway responsiveness and bronchoalveolar lavage (BAL) cell composition in sensitized guinea-pigs after daily inhalation of ovalbumin.
The association between inflammatory cell influx, cell activation status and change of airway responsiveness to acetylcholine (ACh) after daily inhalation of ovalbumin (OA) in sensitized guinea-pigs was investigated. Starting 3 weeks after sensitization (OA at 50 mg/kg s.c.+i.p.) guinea-pigs were exposed daily to 2% OA (10 min; under cover of 0.5 mg/kg mepyramine i.p. 15 min before OA) for 2 weeks. Concentration-response curves (CRCs) for inhaled ACh were performed 24 h after the last OA-challenge and 24 h after another single OA-inhalation 1 week later. CRCs for inhaled ACh were neither affected 24 h after the last OA challenge (daily for two weeks) nor 24 h after another OA-inhalation one week later. In contrast, bronchoalveolar lavage (BAL) from repeatedly OA- sensitized/-challenged guinea-pigs immediately after the last CRC showed a significant increase of total cell count by about tenfold and increases in eosinophils by about 20-fold, neutrophils by 30-fold, macrophages by about fivefold and lymphocytes by about tenfold (P < 0.05, multiple Wilcoxon-test). In contrast, markers of cell activation (EPO, MPO) were significantly decreased (P < 0.05). Methylprednisolone almost completely prevented these changes in increased cell numbers and decreased cell activation (vs OA contr., P < 0.05). The lack of increased airway hyperresponsiveness despite a massive inflammatory cell influx suggests other factors controlling airway responsiveness than inflammation.
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim/Rhein, Mainz, Germany.
H O
HO
Heuer
B
B
Wenz
H M
HM
Jennewein
K
K
Urich
D000109:Acetylcholine / Q000008:administration & dosage; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D047209:Eosinophil Peroxidase; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D007958:Leukocyte Count; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D009195:Peroxidase / Q000032:analysis; D010544:Peroxidases / Q000032:analysis
D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009195:Peroxidase; D000109:Acetylcholine