Co-expression of LPLUNC1 and MUC5B in the bronchiolarized epithelium of usual interstitial pneumonia

Idiopathic Pulmonary Fibrosis (IPF) is an irreversible and progressive lung disease with limited life expectancy after diagnosis. The cause of the condition remains elusive but it has both familial and environmental associations. Histopathological studies of IPF lungs reveal the typical “Usual Interstitial Pneumonia” (UIP) pattern, with epithelial hyperplasia, areas of scarring with fibroblast foci and characteristic morphological abnormalities, including bronchiolization of alveolar ducts, cysts and alveoli. Although it seems likely that bronchiolar abnormalities are caused by changes in epithelial cell differentiation, specific markers of this process remain elusive. By analysis of published array data sets from IPF patients, we identified LPLUNC1 as a potential candidate marker for the disease. This putative innate defence protein is normally expressed in submucosal glands (SMGs) and in a population of MUC5A/C positive goblet cells in the upper airways. Immunohistochemical analysis of lung tissue from patients with UIP revealed strong staining of LPLUNC1 within the bronchiolarized epithelium lining the honeycomb cysts as well as in the mucosubstance filling these regions and dispersed throughout the peripheral lung. The related protein, SPLUNC1 was not co-expressed. MUC5B was localized to the same cells as LPLUNC1, whereas MUC5A/C was found in goblet cells within the airways. The same pattern of staining was not seen in other chronic lung diseases, suggesting a degree of specificity for IPF. Our data support the idea that in UIP, airway epithelial cells develop characteristics of SMGs and suggest that LPLUNC1 may be a useful marker for the disease.