Cytokeratin Expression Patterns in the Rat Respiratory Tract as Markers of Epithelial Differentiation in Inhalation Toxicology. I. Determination of Normal Cytokeratin Expression Patterns in Nose, Larynx, Trachea, and Lung

Abstract

Cytokeratin (CK) polypeptides constitute the intermediate filament cytoskeleton of epithelial cells. The patterns of CK expression can be regarded as specific markers for the epithelial differentiation status. Our objective was to map the cell type-specific CK expression patterns at all representative sites of the respiratory tract of untreated rats to use as a base for the detection of inhalation exposure-related differentiation changes. Using routine paraffin-embedded sections and a panel of well-characterized monoclonal antibodies for immunohistochemistry, we obtained CK staining patterns as follows. Nasal cavity: respiratory epithelium CKI8, CK19 (basal, ciliated, nonciliated cells), CK14, and/or CK15 (basal and nonciliated cells); olfactory epithelium CK18 (basal, mid, apical zones and Bowman's glands), CK14, and CK15 (basal zone); squamous epithelium of ventral meatus CK14, CK15 (basal and supra-basal cells), CK1, 10/11, and CK13 (suprabasal cells); glands and columnar epithelia of vomeronasal organ and nasolacrimal duct CK7 and CK13 in addition to respiratory epithelial CK pattern. Trachea: similar to nasal respiratory epithelium with pronounced CK15 and additional CK7. Larynx: CK14, CK15 (basal, ciliated, nonciliated cells), CK8, CK18, CK19 (not in basal cells), CK4, and CK13 (cuboidal and squamoid cells of ventral half). Lung: bronchial epithelium CK14 and CK15 (basal cells only); bronchial and alveolar epithelium CK7, CK8, CK18, and CK19; bronchiolar epithelium similar but less CK8 and no CK7; pleural mesothelium CK7, CK8, and CK19. This inventory of complex CK expression patterns provides the basis for investigating test substance-related effects in inhalation toxicology, e.g., cigarette smoke-induced changes.