Elastase Causes Secretory Discharge in Bronchi of Hamsters with Elastase-Induced Secretory Cell Metaplasia

Abstract

A single intratracheal instillation of human neutrophil elastase (HNE) into hamsters causes granule discharge from bronchial secretory cells followed by marked accumulation of granules, visible by light microscopy at 21 days and persisting through 18 months. To determine whether persistence of this secretory cell metaplasia (SCM) is due to inability of the metaplastic secretory cells to secrete their granules, hamsters having HNE-induced SCM were challenged with the potent secretagogue HNE. Four groups of 10 hamsters each received 300 pg HNE intratracheally. Twenty-one days later, hamsters were intratracheally treated with HNE or saline; the groups were designated HNE-HNE and HNE-SAL, respectively. Hamsters were killed 2 h or 21 days following the second treatment. Using light microscopy, nucleated epithelial cells were counted in plastic sections of the left main intrapulmonary bronchus. Cells were classified as ciliated (C), basal (B), indeterminate (IN), or secretory. Secretory cells were subcategorized as S₀ (O granules), S₁ (1–4 granules), S₂ (≥ 5 granules with intervening cytoplasm), and S₃ (abundant granules completely filling the cytoplasm). At 2 h, S₃ cell frequency in the HNE-HNE group was 13.0 ± 2.2 (% mean ± SE), significantly lower than in the 2 h HNE-SAL group (31.1 ± 4.5). Concomitantly, higher cell frequencies were seen in the other secrtory categories of the HNE-HNE group compared to the HNE-SAL group; S₂ 17.1 ± 1.9 compared to 9.4 ± 1.9, S₁ 2.4 ± 0.4 compared to 1.1 ± 0.5, and S₀ 2.4 ± 0.5 compared to 1.1 ± 0.5, respectively. The S₃ cell frequency of the 21-day HNE-HNE group was 25.4 ± 4.7, increased significantly compared to the 2 h HNE-HNE group; this change was concomitant with significant decrease in the frequency of the S₀ secretory cells. Cell frequencies of C, B, and IN were not affected by treatment or time. It is concluded that metaplastic secretory cells discbarge their granules in response to HNE; SCM returns to its original state after HNE rechallenge; persistent SCM is not due to the inability of metaplastic secretory cells to discharge their granules.