EFFECT OF DEXAMETHASONE ON ANTIGEN-INDUCED HIGH-MOLECULAR-WEIGHT GLYCOCONJUGATE SECRETION IN ALLERGIC GUINEA-PIGS

The ovalbumin-sensitized guinea pig is commonly used as a small animal model of allergic asthma. This animal model exhibits many of the hall mark characteristics observed in patients afflicted with asthma includ ing nonspecific airway hyperreactivity, airway eosinophilia, early and late phase bronchoconstriction, and plasma extravasation into the air ways. In addition, mucous hypersecretion in the airways of asthmatic p atients is thought to be responsible for the plugging of distal airway s and to contribute to the morbidity and mortality associated with the disease process. In this study we examined whether the allergic guine a pig model exhibits an increase in airway high molecular weight glyco conjugate (HMWG) secretion in response to an antigen challenge and whe ther dexamethasone exerts any modulatory effects upon the response. Ov albumin (OVA)-sensitized guinea pigs were challenged with OVA 2 wk fol lowing the initial exposure. Trachobronchoalveolar lavages (TEAL) were performed, and the samples were assayed for total eosinophil cell num ber, eosinophil peroxidase activity (EPO), and both acidic and neutral HMWG content. Morphometric analysis of mucous-containing cells was al so performed on tissue sections prepared from the trachea, mainstem br onchus, and three lobes of the left lung. Within 24 h of an antigen ch allenge, TEAL samples obtained from the allergic guinea pigs exhibited increases in eosinophil cell number, measured EPO enzyme activity, an d acidic HMWG content compared to TEAL samples prepared from vehicle-e xposed animals. These antigen-induced changes were dependent on the co ncentration of aerosolized OVA administered. Exposing the animals to 0 .3% OVA provoked a 6.23-fold increase in airway eosinophils, 15-fold e levation in TEAL EPO enzyme activity, and 175% increase in TEAL acidic HMWG. No significant changes in TBAL neutral HMWG were measured. The changes in measured EPO activity correlated with the levels of acidic HMWG found in the TEAL samples (r = 0.73, P less than or equal to 0.00 1). The measured increase in TEAL acidic HMWG was time dependent and w as found to be maximal at 2 h post-antigen challenge. Morphometric ana lysis of Alcian blue (pH 2.5)-stained airway sections showed a decline in stored mucosubstances following the antigen exposure, supporting t he notion that the allergic guinea pig model exhibits a mucosecretory component. Pretreating the animals with dexamethasone attenuated the a ntigen-induced release of HMWG and changes in measured EPO activity. I n conclusion, these data indicate that the allergic guinea pig may be a useful model for examining the neural and cellular mechanisms underl ying mucus hypersecretion in individuals afflicted with bronchial asth ma.