Antigen-coated sepharose beads induce airway eosinophilia and airway hyperresponsiveness in cynomolgus monkeys.
A method of inducing sustained airway eosinophilia and airway hyperresponsiveness in primates has been developed. Our method utilizes a series of intratracheal instillations of Ascaris suum-coated sepharose 4B beads (3 x 10(5] administered once a week for four weeks. Five cynomolgus monkeys (Macaca fascicularis) demonstrating a naturally occurring skin and respiratory sensitivity to Ascaris suum extract were studied. Airway cell composition was measured by bronchoalveolar lavage (BAL), and airway responsiveness was determined as the bronchoconstrictor response to inhaled methacholine. Ascaris suum bead administration resulted in a transient increase in total cells recovered by BAL (2.4 +/- 0.4 to 8.7 +/- 2.5 x 10(5) cells/ml, p less than 0.05) and a selective increase in BAL eosinophils (17 +/- 6 to 916 +/- 158 x 10(3) cells/ml, p less than 0.05). Increases in airway responsiveness were concurrent with the increase in airway eosinophils. These observations show that airway eosinophilia is associated with airway hyperresponsiveness in primates. Furthermore, this new model is a novel experimental system in which the underlying mechanisms in the pathogenesis of airway hyperresponsiveness can be investigated.
Gundel
R H
RH
Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
Gerritsen
M E
ME
Wegner
C D
CD
D000403:Airway Resistance; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage*; D001200:Ascaris / Q000276:immunology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000166:cytology*; D008252:Macaca fascicularis; D008264:Macrophages / Q000166:cytology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D008863:Microspheres; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D012137:Respiratory System / Q000166:cytology*; D012685:Sepharose
D000947:Antigens, Helminth; D008688:Methacholine Compounds; D016210:Methacholine Chloride; D012685:Sepharose