Airway submucosal gland serous cell dysfunction in vitamin A-deficient mice

Abstract

Vitamin A deficiency (VAD) alters the phenotype of airway epithelium and attenuates the epithelial defense system, and many studies have reported the association of VAD with respiratory disease. VAD also affects the phenotype of exocrine glands and airway submucosal glands (SMGs) play a key role in innate immunity by producing mucus and antimicrobial peptides. However, there are only a few reports on the relationship between VAD and SMGs. In this study, we investigated changes in SMGs in a mouse model of VAD. One group of C57BL/6 mice was fed a vitamin A-devoid diet and the other group was fed a control diet. The areas of serous and mucous cells of SMGs were measured in 4-, 8-, and 20-wk-old male mice. The volume and lysozyme concentration of glandular secretions were also measured in 8-wk-old male mice. The two groups did not differ in body weight or general morbidity at 3 to 10 wk of age, although serum retinol concentrations were greater in the control mice than in the VAD mice after 4 wk. Upon histological evaluation, we found that the areal ratio of serous cells to total SMG cells was significantly lower after 8 wk in the VAD mice compared to the control mice although the total area of SMGs did not differ between groups throughout the 20 wk experiment. The number of secretory bubbles did not differ between the groups but total secretion volume was reduced by 35% in 8-wk-old VAD mice compared to controls. Furthermore, the concentration of lysozyme in secretions from 8-wk-old VAD mice was also less than in controls, compounding the effect of diminished secretion volume. In this study, we found serous cell hypotrophy/hypoplasia and dysfunction in VAD mice, which may contribute to the susceptibility to airway infection linked to VAD.