PLUNC: a multifunctional surfactant of the airways

Bartlett, Jennifer; Gakhar, Lokesh; Penterman, Jon; Singh, Pradeep K; Mallampalli, Rama K.; Porter, Edith; McCray, Paul B.

doi:10.1042/bst0391549

Cited by 13 publications

(17 citation statements)

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“…It was initially hypothesized to express antimicrobial functions, and has been shown to inhibit the growth of multiple pathogens (16-19), inhibit biofilm formation, and possess surfactant properties (20,21). Although most studies of SPLUNC1 have focused on these antimicrobial effects, SPLUNC1 also regulates the epithelial sodium channel (ENaC) to maintain airway surface liquid depth, affects mucociliary clearance, and regulates inflammation, thereby limiting allergic airway inflammation (10, 22-24).…”

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confidence: 99%

Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity

Britto

Liu

Curran

et al. 2013

Am J Respir Cell Mol Biol

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Short palate, lung, and nasal epithelial clone-1 (SPLUNC1) is a protein abundantly expressed by the respiratory epithelium of the proximal lower respiratory tract, a site of great environmental exposure. Previous studies showed that SPLUNC1 exerts antimicrobial effects, regulates airway surface liquid and mucociliary clearance, and suppresses allergic airway inflammation. We studied SPLUNC1 to gain insights into its role in host defense. In the lower respiratory tract, concentrations of SPLUNC1 are high under basal conditions. In models of pneumonia caused by common respiratory pathogens, and in Th1-induced and Th2-induced airway inflammation, SPLUNC1 secretion is markedly reduced. Pathogen-associated molecular patterns and IFN-g act directly on airway epithelial cells to inhibit SPLUNC1 mRNA expression. Thus, SPLUNC1 is quickly suppressed during infection, in response to an insult on the epithelial surface. These experiments highlight the finely tuned fluctuations of SPLUNC1 in response to exposures in the respiratory tract, and suggest that the loss of SPLUNC1 is a crucial feature of host defense across airbreathing animal species.Keywords: SPLUNC1; inflammation; innate; immunity; mucosaThe respiratory tract continuously interacts with environmental irritants and pathogens. These stimuli constitute part of an intricate network of signals that activate host defenses. Airway epithelial cells participate actively in this process by producing antimicrobial and immune mediators that maintain homeostasis during steady-state conditions, and promote inflammation during injury.The palate, lung, and nasal epithelial clone (PLUNC) genes are members of the bactericidal permeability-increasing protein foldcontaining (BPIF)/PLUNC protein family (1, 2). These genes are focally expressed by epithelial cells throughout the respiratory tracts of multiple air-breathing vertebrates (3). In total, 11 human genes and 14 murine genes have been described to date, located within a single locus on chromosome 20 and chromosome 2, respectively (4, 5). These genes code for the PLUNC proteins, which are classified into six short and eight long PLUNCs, based on their lengths.Short PLUNC 1 (SPLUNC1) is a 25-kD protein secreted by epithelial cells in the upper airway and proximal lower respiratory tract (3, 6-10). SPLUNC1 is readily detected in human saliva and in nasal and bronchial epithelial washings at concentrations ranging from 34.7 ng/ml to 13.8 mg/ml (6, 10-12). In tracheal epithelial-cell supernatants SPLUNC1 constituted 10% of the total soluble protein, making it one of the most highly expressed proteins produced by airway epithelial cells (7).SPLUNC1 shares structural similarities with the immunomodulatory proteins bactericidal permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (4, 13-15). It was initially hypothesized to express antimicrobial functions, and has been shown to inhibit the growth of multiple pathogens (16-19), inhibit biofilm formation, and possess surfactant properties (20,21). Although mos...

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confidence: 99%

Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity

Britto

Liu

Curran

et al. 2013

Am J Respir Cell Mol Biol

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“…Palate Lung Nasal Clone, also known as SPLUNC1 (S ¼ secreted), PLUNC1, LUNX (lung-specific X protein), NASG (nasopharyngeal carcinoma-related protein), or SPURT (secretory protein in upper respiratory tracts) is a secreted glycoprotein of approximately 25 kDa that is an important protein involved in innate immunity. 7 It is highly expressed in healthy airways, goblet cells, and minor mucosal glands of the respiratory tract and oral cavity, surface epithelium ciliated cells, and human submucosal gland serous cells, 8,9 and with that at sites of great environmental exposure. Because of its physicochemical properties (distinct hydrophobicity) and cellular distribution, PLUNC belongs to the family of surfactant proteins and significantly contributes to the overall surface tension in airway epithelial secretions.…”

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confidence: 99%

Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three-Dimensional Structure, Immune Activation, and Involvement in Dry Eye Disease (DED)

Schicht

Rausch

Beron

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Schicht M, Rausch F, Beron M, et al. Palate lung nasal clone (PLUNC), a novel protein of the tear film: three-dimensional structure, immune activation, and involvement in dry eye disease (DED). Invest Ophthalmol Vis Sci. 2015;56:7312-7323. DOI:10.1167/iovs.15-17560 PURPOSE. Palate Lung Nasal Clone (PLUNC) is a hydrophobic protein belonging to the family of surfactant proteins that is involved in fluid balance regulation of the lung. Moreover, it is known to directly act against gram-negative bacteria. The purpose of this study was to investigate the possible expression and antimicrobial role of PLUNC at the healthy ocular surface and in tears of patients suffering from dry eye disease (DED).METHODS. Bioinformatics and biochemical and immunologic methods were combined to elucidate the structure and function of PLUNC at the ocular surface. Tissue-specific localization was performed by using immunohistochemistry. The PLUNC levels in tear samples from non-Sjögren's DED patients with moderate dry eye suffering either from hyperevaporation or tear deficiency were analyzed by ELISA and compared with tears from healthy volunteers.RESULTS. Palate Lung Nasal Clone is expressed under healthy conditions at the ocular surface and secreted into the tear film. Protein modeling studies and molecular dynamics simulations performed indicated surface activity of PLUNC. In vitro experiments revealed that proinflammatory cytokines and bacterial supernatants have only a slight effect on the expression of PLUNC in HCE and HCjE cell lines. In tears from DED patients, the PLUNC concentration is significantly increased (7-fold in evaporative dry eye tears and 17-fold in tears from patients with tear deficiency) compared with healthy subjects. CONCLUSIONS.The results show that PLUNC is a protein of the tear film and suggest that it plays a role in fluid balance and surface tension regulation at the ocular surface.

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“…(17) SPLUNC1 has also been shown to have an anti-inflammatory function in exogenous microbe-induced respiratory infection, such as K. pneumoniae, (18) Mycoplasma pneumoniae, (19) P. aeruginosa, and Epstein-Barr virus. (20) Additionally, SPLUNC1 could also regulate ion/mucus transport and hydration levels in the lung, (21) lower surface tension by its surfactant-like properties, (22) and act as an inflammatory mediator. The earlier studies demonstrated that SPLUNC1 was associated with tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

SPLUNC1 Is a Significant Marker in Pleural Effusion from Lung Cancer Compared to Tuberculosis

Xue

Yan

et al. 2015

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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SPLUNC1 (Short palate, lung and nasal epithelium clone1) protein is an abundant secretory product of epithelia present throughout the conducting airways. Although its function is still not fully known, most studies have focused on its defensive effect in the infection of human airways and its potential to serve as a molecular marker for lung cancer. In this study, we further evaluated the SPLUNC1 expression in patients with lung disease to explore its role in cancer or tuberculosis at the protein level. We generated a panel of antibodies by using protein from a eukaryotic expression system as the immunogen to mice. It was the panel of SPLUNC1 monoclonal antibodies that allowed us to comparatively determine SPLUNC1 protein in lung cancer and tuberculosis infection by detecting sera and pleural effusion other than airway surface. The results showed that the SPLUNC1 level was not significantly changed either from sera of lung cancer or control. There was a significant increase in pleural effusion from lung cancer when compared to tuberculosis. These results indicate that SPLUNC1 may be a useful marker for tracing lung cancer cells, based on its epithelial origin property in pleural effusion.

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PLUNC: a multifunctional surfactant of the airways

Cited by 13 publications

References 0 publications

Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity

Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity

Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three-Dimensional Structure, Immune Activation, and Involvement in Dry Eye Disease (DED)

SPLUNC1 Is a Significant Marker in Pleural Effusion from Lung Cancer Compared to Tuberculosis

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