Kinetics and quantitation of eosinophil and neutrophil recruitment to allergic lung inflammation in a brown Norway rat model.

Abstract

We quantitated neutrophil and eosinophil migration into lung parenchyma using specific peroxidase enzyme assays, and into the bronchoalveolar compartment by bronchoalveolar lavage (BALF), in sensitized brown Norway (BN), Fischer, and Lewis rats and also assessed the lungs by histopathology. Fourteen days after sensitization with ovalbumin (OA in alum [given subcutaneously] and OA with Bordetella pertussis [given intraperitoneally]), rats were challenged with an OA aerosol for 1 h. In BN rats, there was marked perivascular and peribronchial edema, focal hemorrhages, and increase in lung wet weight and BALF protein content, accompanied by neutrophilic infiltration at 3-14 h postchallenge. Few eosinophils were seen at 14 h in lung tissue or in BALF. Neutrophils peaked at 24 h in parenchyma ([94 +/- 7] x 10[6]) and in BALF ([2.7 +/- 0.4] x 10[6]) and declined rapidly thereafter. Marked eosinophil infiltration into parenchyma was apparent by 24 h. Eosinophil accumulation peaked at 48 h in parenchyma ([127 +/- 18] x 10[6]) and at 72 h in BALF ([10 +/- 2.4] x 10[6]), comprising up to 85% of lavage cells at this time. Lung eosinophilia persisted for at least 6 d with only a slow decline or clearance, not approximating baseline until day 13 after challenge. Histopathology showed peribronchial and interstitial eosinophilic pneumonia, most severe on day 3. In contrast to the BN rats, essentially no pulmonary inflammation was observed in Lewis and Fischer rats. This model in the BN rat, and the specific peroxidase assays for quantitating tissue eosinophils and neutrophils, should be useful for investigating the regulation of allergen-induced eosinophil and neutrophil migration into and clearance from the lung.