Human LPLUNC1 is a secreted product of goblet cells and minor glands of the respiratory and upper aerodigestive tracts

Abstract

Long PLUNC1 (LPLUNC1, C20orf114) is a member of a family of poorly described proteins (PLUNCS) expressed in the upper respiratory tract and oral cavity, which may function in host defence. Although it is one of the most highly expressed genes in the upper airways and has been identified in sputum and nasal secretions by proteomic studies, localisation of LPLUNC1 protein has not yet been described. We developed affinity purified antibodies and localised the protein in tissues of the human respiratory tract, oro- and nasopharynx. We have complemented these studies with analysis of LPLUNC1 expression in primary human lung cell cultures and used Western blotting to study the protein in cell culture secretions and in BAL. LPLUNC1 is a product of a population of goblet cells in the airway epithelium and nasal passages and is also present in airway submucosal glands and minor glands of the oral and nasal cavities. The protein is not expressed in peripheral lung epithelial cells. LPLUNC1 is present in bronchoalveolar lavage fluid as two glycosylated isoforms and primary airway epithelial cells produce identical proteins as they undergo mucociliary differentiation. Our results suggest that LPLUNC1 is an abundant, secreted product of goblet cells and minor mucosal glands of the respiratory tract and oral cavity and suggest that the protein functions in the complex milieu that protects the mucosal surfaces in these locations.Electronic supplementary materialThe online version of this article (doi:10.1007/s00418-010-0683-0) contains supplementary material, which is available to authorized users.

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

“…It is likely that sputum BPIFB1 levels reflect the homeostasis of the respiratory epithelium and may be upregulated in COPD as a result of smoking, chronic infection, and enhanced immune responses. We have previously shown that BPIFB1 is found in a population of airway goblet cells (4). It is therefore not surprising that sputum BPIFB1 levels are elevated in more severe COPD where ciliated epithelial cells are replaced by goblet cells as a physiological response to increased airway irritation.…”

“…Serial sections (4 m) were cut from formalin-fixed and paraffin-embedded tissue and stained as previously described (4,5,7). The following antibodies were used in this study: rabbit polyclonal antibodies against BPIFB1 (final dilution of 1:600) (4) and rabbit polyclonal antibodies against MUC5B (SC-20119, Santa Cruz Biotechnology, final dilution 1:500).…”

“…However, they have distinct expression patterns. BPIFB1 is localized in a population of goblet cells in the nasal passage and airway epithelium and within the serous cells of the airway submucosal glands, whereas BPIFA1 is localized to a population of nonciliated epithelial cells and in the mucous cells of the submucosal glands (4,6,7). Both proteins are secreted into the airway lumen and are among the most abundant proteins in respiratory tract secretions (4).…”

“…BPIFB1 is localized in a population of goblet cells in the nasal passage and airway epithelium and within the serous cells of the airway submucosal glands, whereas BPIFA1 is localized to a population of nonciliated epithelial cells and in the mucous cells of the submucosal glands (4,6,7). Both proteins are secreted into the airway lumen and are among the most abundant proteins in respiratory tract secretions (4). BPIFB1 has previously been identified in the proteome of nasal mucous (11) and induced sputum (10,22,24), and elevated levels of the protein were detected in a proteomic study of BALF from asthmatic patients after segmental allergen challenge (39).…”

Histochemistry and cell biology: the annual review 2010

“…Proteomic studies have reported LPLUNC1 to be in nasal secretions, bronchoalveolar lavage and sputum (Casado et al 2005;Nicholas et al 2006;Wu et al 2005) and to be a major secreted product of cultured tracheobronchial epithelial cells (Candiano et al 2007;Kesimer et al 2009). Immunohistochemistry was therefore applied to address expression of LPLUNC1 in tissues of the human respiratory tract, oro-and nasopharynx (Bingle et al 2010). LPLUNC1 was found to be abundantly expressed in a population of goblet cells in the upper respiratory tract and was strongly expressed in airway submucosal glands and a range of minor glands present in the oral cavity and nasopharynx, suggesting a role for LPLUNC1 in mucosal surface protection at these sites.…”