EFFECT OF EOSINOPHIL PEROXIDASE ON AIRWAY EPITHELIAL PERMEABILITY IN THE GUINEA-PIG

Increased numbers of eosinophils and increased concentrations of plasm a proteins have been found in the airways of patients with mild asthma . We used an intact guinea pig trachea model to investigate the role o f eosinophil peroxidase (EPO) in altering the function of the airway e pithelial barrier. EPO in the presence of hydrogen peroxide (H2O2) and bromide (Br-) catalyzes the production of hypobromous acid (HOBr), wh ich is felt to have a toxic effect on airway epithelial cells. An inta ct guinea pig trachea was mounted on an apparatus in a way that would allow the tracheal epithelium to be exposed to different solutions. Fo llowing these exposures, a test solution containing C-14-sucrose (S), H-3-inulin (I), and FITC-dextran-20 (D) was placed in the tracheal lum en and positioned in the center of the segment for 90 minutes. Flux of these molecules across the epithelial barrier into a bath was measure d, and the permeability (P) was calculated for each molecule to quanti fy epithelial barrier function. Light and electron micrographic studie s were performed to assess cellular damage. We found that there was a dose response to EPO (in the presence of fixed amounts of H2O2 and Br- ). EPO at 7.3 x 10(-7) M caused no increase in P over controls (Ringer 's solution alone) for S, I, or D (P > 0.05), whereas EPO at 2.7 x 10( -6) M caused a significant increase in P over controls (P = 0.008) for all test molecules. Light and electron micrographs of the latter trac heas showed no evidence of microscopic changes despite the increased P . Further testing verified that the increase in permeability was cause d by the EPO catalyzed reaction and not the individual substrates them selves, and that the reaction was inhibited by a peroxidase inhibitor. We conclude that EPO can alter the barrier function of the airway epi thelium before gross cellular damage becomes visible. We hypothesize t hat changes in the tight junctions are responsible for the alteration in the barrier function of the airway epithelium and that this may pla y an important role in the pathophysiology of mild asthma. Pediatr Pul monol, 1996; 21:159-166. (C) 1996 Wiley-Liss, Inc.