Immunohistochemical Characteristics of Surfactant Proteins A, B, C and D in Inflammatory and Tumorigenic Lung Lesions of F344 Rats

Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically. Formalin fixed paraffin embedded (FFPE) lung samples featuring inflammation were obtained with a rat quartz instillation model, and neoplastic lesions, hyperplasias and adenomas, were obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz instillation model, male 10-week old F344 rats were exposed by intratracheal instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was initiated by DHPN in drinking water for 2 weeks, and the animals were then sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas, were observed with DHPN, and inflammation was observed with quartz. The expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP-B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A and SP-D were observed in mucus or exudates in inflammatory alveoli. These results suggest the possibility that SP-B and SP-C are related to lung tumorigenesis.

[1]  J. López-Barneo,et al.  Effect of hypoxia on lung gene expression and proteomic profile: insights into the pulmonary surfactant response. , 2014, Journal of proteomics.

[2]  Murugesan V. S. Rajaram,et al.  Molecular composition of the alveolar lining fluid in the aging lung , 2014, AGE.

[3]  Jie Ma,et al.  Genotype-phenotype correlation in Chinese patients with pulmonary mixed type adenocarcinoma: Relationship between histologic subtypes, TITF-1/SP-A expressions and EGFR mutations. , 2014, Pathology, research and practice.

[4]  K. Saoo,et al.  Napsin A is possibly useful marker to predict the tumorigenic potential of lung bronchiolo-alveolar hyperplasia in F344 rats. , 2014, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[5]  S. Lam,et al.  Budesonide/Formoterol Enhances the Expression of Pro Surfactant Protein-B in Lungs of COPD Patients , 2013, PloS one.

[6]  S. Hanash,et al.  Pro-surfactant protein B as a biomarker for lung cancer prediction. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  H. Asamura,et al.  Expression of Squamous Cell Carcinoma Markers and Adenocarcinoma Markers in Primary Pulmonary Neuroendocrine Carcinomas , 2013, Applied immunohistochemistry & molecular morphology : AIMM.

[8]  Robert B Sim,et al.  Ligands and receptors of lung surfactant proteins SP-A and SP-D. , 2013, Frontiers in bioscience.

[9]  J. Ledford,et al.  Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages. , 2013, The American journal of pathology.

[10]  V. Čapkun,et al.  IMP3 can predict aggressive behaviour of lung adenocarcinoma , 2012, Diagnostic Pathology.

[11]  M. Kadivar,et al.  Applications and Limitations of Immunohistochemical Expression of “Napsin-A” in Distinguishing Lung Adenocarcinoma From Adenocarcinomas of Other Organs , 2012, Applied immunohistochemistry & molecular morphology : AIMM.

[12]  A. Jemal,et al.  Cancer statistics, 2011 , 2011, CA: a cancer journal for clinicians.

[13]  D. Clark,et al.  The utility of napsin‐A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas , 2010, Cancer cytopathology.

[14]  J. Pérez-Gil,et al.  Pulmonary surfactant pathophysiology: current models and open questions. , 2010, Physiology.

[15]  M. Pino,et al.  Proliferative and Nonproliferative Lesions of the Rat and Mouse Respiratory Tract , 2009, Toxicologic pathology.

[16]  K. Saoo,et al.  Molecular analysis of carcinogen-induced rodent lung tumors: Involvement of microRNA expression and Krαs or Egfr mutations. , 2009, Molecular medicine reports.

[17]  D. Feldser,et al.  Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma , 2009, Nature.

[18]  K. Saoo,et al.  Lung Carcinogenic Bioassay of CuO and TiO2 Nanoparticles with Intratracheal Instillation Using F344 Male Rats , 2009, Journal of toxicologic pathology.

[19]  K. Saoo,et al.  An Intratracheal Instillation Bioassay System for Detection of Lung Toxicity Due to Fine Particles in F344 Rats , 2009, Journal of toxicologic pathology.

[20]  K. Saoo,et al.  Lung Toxicity of 16 Fine Particles on Intratracheal Instillation in a Bioassay Model Using F344 Male Rats , 2008, Toxicologic pathology.

[21]  M. Leitges,et al.  Surfactant Protein A Activation of Atypical Protein Kinase C ζ in IκB-α-Dependent Anti-Inflammatory Immune Regulation1 , 2007, The Journal of Immunology.

[22]  K. Imaida,et al.  Detection of Carcinogenic and Modifying Potentials by Test Compounds Using a Mouse Lung Carcinogenesis Bioassay , 2007 .

[23]  S. Hecht,et al.  Indole-3-carbinol inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo(a)pyrene-induced lung tumorigenesis in A/J mice and modulates carcinogen-induced alterations in protein levels. , 2007, Cancer research.

[24]  V. Cottin,et al.  Alveolar type II cells isolated from pulmonary adenocarcinoma: a model for JSRV expression in vitro. , 2007, American journal of respiratory cell and molecular biology.

[25]  K. Saoo,et al.  Bioassay by intratracheal instillation for detection of lung toxicity due to fine particles in F344 male rats. , 2007, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[26]  H. Maeta,et al.  Establishment of a Bioassay System for Detection of Lung Toxicity Due to Fine Particle Instillation: Sequential Histopathological Changes with Acute and Subacute Lung Damage Due to Intratracheal Instillation of Quartz in F344 Male Rats , 2005 .

[27]  D. Heederik,et al.  Lung function decrease in relation to pneumoconiosis and exposure to quartz-containing dust in construction workers. , 2003, American journal of industrial medicine.

[28]  J. Whitsett,et al.  Distinct Effects of Surfactant Protein A or D Deficiency During Bacterial Infection on the Lung1 , 2000, The Journal of Immunology.

[29]  J. Taylor,et al.  Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[30]  Dietel,et al.  Thyroid transcription factor‐1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B , 2000, Histopathology.

[31]  J. Whitsett,et al.  Surfactant Protein B Corrects Oxygen-Induced Pulmonary Dysfunction in Heterozygous Surfactant Protein B–Deficient Mice , 1999, Pediatric Research.

[32]  J. Whitsett,et al.  Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. , 1999, Human pathology.

[33]  J. Whitsett,et al.  Surfactant protein-A enhances respiratory syncytial virus clearance in vivo. , 1999, The Journal of clinical investigation.

[34]  J. Pérez-Gil,et al.  Interfacial properties of surfactant proteins. , 1998, Biochimica et biophysica acta.

[35]  R. Lauro,et al.  Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. , 1996, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[36]  P. Venge,et al.  Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis. , 1993, The American review of respiratory disease.

[37]  D. Voelker,et al.  Rat surfactant protein D enhances the production of oxygen radicals by rat alveolar macrophages. , 1992, The Biochemical journal.

[38]  A. Gazdar,et al.  Glucocorticoids regulate surfactant protein synthesis in a pulmonary adenocarcinoma cell line. , 1989, The American journal of physiology.

[39]  S. Benson,et al.  Regulation of lung fibroblast proliferation and protein synthesis by bronchiolar lavage in experimental silicosis. , 1986, Environmental research.

[40]  R. Notter,et al.  Hydrophobic Surfactant-Associated Protein in Whole Lung Surfactant and Its Importance for Biophysical Activity in Lung Surfactant Extracts Used for Replacement Therapy , 1986, Pediatric Research.

[41]  I. Adamson,et al.  The role of cell injury and the continuing inflammatory response in the generation of silicotic pulmonary fibrosis , 1984, The Journal of pathology.

[42]  P. Illei,et al.  Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. , 2010, Human pathology.

[43]  M. Leitges,et al.  Surfactant protein A activation of atypical protein kinase C zeta in IkappaB-alpha-dependent anti-inflammatory immune regulation. , 2007, Journal of immunology.

[44]  S. Guttentag,et al.  Cysteine protease activity is required for surfactant protein B processing and lamellar body genesis. , 2003, American journal of respiratory cell and molecular biology.

[45]  P. R. Miles,et al.  Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[46]  J. Verhoef,et al.  Pulmonary surfactant protein A enhances the host-defense mechanism of rat alveolar macrophages. , 1990, American journal of respiratory cell and molecular biology.