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Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis

Authors: Masahiko Shigemura, Yasuyuki Nasuhara, Satoshi Konno, Chikara Shimizu, Kazuhiko Matsuno, Etsuro Yamaguchi, Masaharu Nishimura

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

Serum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases. However, there remain some limitations due to a lack of information on the factors contributing to increased levels of serum KL-6. This study was designed to investigate the factors contributing to increased levels of serum KL-6 by molecular analysis.

Methods

Western blot analysis using anti-KL-6 antibody was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum obtained from 128 subjects with sarcoidosis.

Results

KL-6/MUC1 in BALF showed three bands and five band patterns. These band patterns were associated with the MUC1 genotype and the KL-6 levels. KL-6/MUC1 band patterns in serum were dependent on molecular size class in BALF. Significantly increased levels of serum KL-6, serum/BALF KL-6 ratio and serum soluble interleukin 2 receptor were observed in the subjects with influx of high molecular size KL-6/MUC1 from the alveoli to blood circulation. The multivariate linear regression analysis involving potentially relevant variables such as age, gender, smoking status, lung parenchymal involvement based on radiographical stage and molecular size of KL-6/MUC1 in serum showed that the molecular size of KL-6/MUC1 in serum was significant independent determinant of serum KL-6 levels.

Conclusions

The molecular structural variants of KL-6/MUC1 and its leakage behavior affect serum levels of KL-6 in sarcoidosis. This information may assist in the interpretation of serum KL-6 levels in sarcoidosis.
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Literature
1.
go back to reference Kohno N, Akiyama M, Kyoizumi S, Hakoda M, Kobuke K, Yamakido M: Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. Jpn J Clin Oncol. 1988, 18 (3): 203-216.PubMed Kohno N, Akiyama M, Kyoizumi S, Hakoda M, Kobuke K, Yamakido M: Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. Jpn J Clin Oncol. 1988, 18 (3): 203-216.PubMed
2.
go back to reference Hirasawa Y, Kohno N, Yokoyama A, Inoue Y, Abe M, Hiwada K: KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts. Am J Respir Cell Mol Biol. 1997, 17 (4): 501-507.CrossRefPubMed Hirasawa Y, Kohno N, Yokoyama A, Inoue Y, Abe M, Hiwada K: KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts. Am J Respir Cell Mol Biol. 1997, 17 (4): 501-507.CrossRefPubMed
3.
go back to reference Hattrup CL, Gendler SJ: Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol. 2008, 70: 431-457. 10.1146/annurev.physiol.70.113006.100659.CrossRefPubMed Hattrup CL, Gendler SJ: Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol. 2008, 70: 431-457. 10.1146/annurev.physiol.70.113006.100659.CrossRefPubMed
4.
go back to reference Brayman M, Thathiah A, Carson DD: MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol. 2004, 2: 4-10.1186/1477-7827-2-4.CrossRefPubMedPubMedCentral Brayman M, Thathiah A, Carson DD: MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol. 2004, 2: 4-10.1186/1477-7827-2-4.CrossRefPubMedPubMedCentral
5.
go back to reference Ohtsuki Y, Fujita J, Hachisuka Y, Uomoto M, Okada Y, Yoshinouchi T, Lee GH, Furihata M, Kohno N: Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia. Med Mol Morphol. 2007, 40 (4): 198-202. 10.1007/s00795-007-0382-7.CrossRefPubMed Ohtsuki Y, Fujita J, Hachisuka Y, Uomoto M, Okada Y, Yoshinouchi T, Lee GH, Furihata M, Kohno N: Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia. Med Mol Morphol. 2007, 40 (4): 198-202. 10.1007/s00795-007-0382-7.CrossRefPubMed
6.
go back to reference Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K: KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis. 1993, 148 (3): 637-642. 10.1164/ajrccm/148.3.637.CrossRefPubMed Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y, Yokoyama A, Hamada H, Fujioka S, Hiwada K: KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis. 1993, 148 (3): 637-642. 10.1164/ajrccm/148.3.637.CrossRefPubMed
7.
go back to reference Goto K, Kodama T, Sekine I, Kakinuma R, Kubota K, Hojo F, Matsumoto T, Ohmatsu H, Ikeda H, Ando M: Serum levels of KL-6 are useful biomarkers for severe radiation pneumonitis. Lung Cancer. 2001, 34 (1): 141-148. 10.1016/S0169-5002(01)00215-X.CrossRefPubMed Goto K, Kodama T, Sekine I, Kakinuma R, Kubota K, Hojo F, Matsumoto T, Ohmatsu H, Ikeda H, Ando M: Serum levels of KL-6 are useful biomarkers for severe radiation pneumonitis. Lung Cancer. 2001, 34 (1): 141-148. 10.1016/S0169-5002(01)00215-X.CrossRefPubMed
8.
go back to reference Ohnishi H, Yokoyama A, Yasuhara Y, Watanabe A, Naka T, Hamada H, Abe M, Nishimura K, Higaki J, Ikezoe J: Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003, 58 (10): 872-875. 10.1136/thorax.58.10.872.CrossRefPubMedPubMedCentral Ohnishi H, Yokoyama A, Yasuhara Y, Watanabe A, Naka T, Hamada H, Abe M, Nishimura K, Higaki J, Ikezoe J: Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax. 2003, 58 (10): 872-875. 10.1136/thorax.58.10.872.CrossRefPubMedPubMedCentral
9.
go back to reference Sakamoto K, Taniguchi H, Kondoh Y, Johkoh T, Sumikawa H, Kimura T, Nishiyama O, Kato K, Kataoka K, Ono K: Serum KL-6 in fibrotic NSIP: Correlations with physiologic and radiologic parameters. Respir Med. 2010, 104 (1): 127-133. 10.1016/j.rmed.2009.08.011.CrossRefPubMed Sakamoto K, Taniguchi H, Kondoh Y, Johkoh T, Sumikawa H, Kimura T, Nishiyama O, Kato K, Kataoka K, Ono K: Serum KL-6 in fibrotic NSIP: Correlations with physiologic and radiologic parameters. Respir Med. 2010, 104 (1): 127-133. 10.1016/j.rmed.2009.08.011.CrossRefPubMed
10.
go back to reference Kobayashi J, Kitamura S: Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest. 1996, 109 (5): 1276-1282. 10.1378/chest.109.5.1276.CrossRefPubMed Kobayashi J, Kitamura S: Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest. 1996, 109 (5): 1276-1282. 10.1378/chest.109.5.1276.CrossRefPubMed
11.
go back to reference Janssen R, Sato H, Grutters JC, Bernard A, van Velzen-Blad H, du Bois RM, van den Bosch JM: Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis. Chest. 2003, 124 (6): 2119-2125. 10.1378/chest.124.6.2119.CrossRefPubMed Janssen R, Sato H, Grutters JC, Bernard A, van Velzen-Blad H, du Bois RM, van den Bosch JM: Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis. Chest. 2003, 124 (6): 2119-2125. 10.1378/chest.124.6.2119.CrossRefPubMed
12.
go back to reference Miyoshi S, Hamada H, Kadowaki T, Hamaguchi N, Ito R, Irifune K, Higaki J: Comparative evaluation of serum markers in pulmonary sarcoidosis. Chest. 2010, 137 (6): 1391-1397. 10.1378/chest.09-1975.CrossRefPubMed Miyoshi S, Hamada H, Kadowaki T, Hamaguchi N, Ito R, Irifune K, Higaki J: Comparative evaluation of serum markers in pulmonary sarcoidosis. Chest. 2010, 137 (6): 1391-1397. 10.1378/chest.09-1975.CrossRefPubMed
13.
go back to reference Honda K, Okada F, Ando Y, Mori H, Umeki K, Ishii H, Kadota J, Ando M, Miyazaki E, Kumamoto T: Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis. Br J Radiol. 2011, 84 (999): 229-235. 10.1259/bjr/65287605.CrossRefPubMedPubMedCentral Honda K, Okada F, Ando Y, Mori H, Umeki K, Ishii H, Kadota J, Ando M, Miyazaki E, Kumamoto T: Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis. Br J Radiol. 2011, 84 (999): 229-235. 10.1259/bjr/65287605.CrossRefPubMedPubMedCentral
14.
go back to reference Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, Eklund A, Kitaichi M, Lynch J, Rizzato G: ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999, 16 (2): 149-173.PubMed Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, Eklund A, Kitaichi M, Lynch J, Rizzato G: ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999, 16 (2): 149-173.PubMed
15.
go back to reference Ligtenberg MJ, Vos HL, Gennissen AM, Hilkens J: Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. J Biol Chem. 1990, 265 (10): 5573-5578.PubMed Ligtenberg MJ, Vos HL, Gennissen AM, Hilkens J: Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. J Biol Chem. 1990, 265 (10): 5573-5578.PubMed
16.
go back to reference Imbert Y, Foulks GN, Brennan MD, Jumblatt MM, John G, Shah HA, Newton C, Pouranfar F, Young WW: MUC1 and estrogen receptor alpha gene polymorphisms in dry eye patients. Exp Eye Res. 2009, 88 (3): 334-338. 10.1016/j.exer.2008.05.019.CrossRefPubMed Imbert Y, Foulks GN, Brennan MD, Jumblatt MM, John G, Shah HA, Newton C, Pouranfar F, Young WW: MUC1 and estrogen receptor alpha gene polymorphisms in dry eye patients. Exp Eye Res. 2009, 88 (3): 334-338. 10.1016/j.exer.2008.05.019.CrossRefPubMed
17.
go back to reference Janssen R, Kruit A, Grutters JC, Ruven HJ, Gerritsen WB, van den Bosch JM: The mucin-1 568 adenosine to guanine polymorphism influences serum Krebs von den Lungen-6 levels. Am J Respir Cell Mol Biol. 2006, 34 (4): 496-499. 10.1165/rcmb.2005-0151OC.CrossRefPubMed Janssen R, Kruit A, Grutters JC, Ruven HJ, Gerritsen WB, van den Bosch JM: The mucin-1 568 adenosine to guanine polymorphism influences serum Krebs von den Lungen-6 levels. Am J Respir Cell Mol Biol. 2006, 34 (4): 496-499. 10.1165/rcmb.2005-0151OC.CrossRefPubMed
18.
go back to reference Zhou Y, Yamaguchi E, Fukui Y, Konno S, Maeda Y, Kimata K, Nishimura M: Enhanced expression of interleukin-18 receptor alpha chain by CD4+ T cells in sarcoidosis. Chest. 2005, 128 (4): 2497-2503. 10.1378/chest.128.4.2497.CrossRefPubMed Zhou Y, Yamaguchi E, Fukui Y, Konno S, Maeda Y, Kimata K, Nishimura M: Enhanced expression of interleukin-18 receptor alpha chain by CD4+ T cells in sarcoidosis. Chest. 2005, 128 (4): 2497-2503. 10.1378/chest.128.4.2497.CrossRefPubMed
19.
go back to reference Shigemura M, Nasuhara Y, Konno S, Hattori T, Shimizu C, Matsuno K, Nishimura M: Levels of transferrin in bronchoalveolar lavage fluid in sarcoidosis. Lung. 2010, 188 (2): 151-157. 10.1007/s00408-009-9218-7.CrossRefPubMed Shigemura M, Nasuhara Y, Konno S, Hattori T, Shimizu C, Matsuno K, Nishimura M: Levels of transferrin in bronchoalveolar lavage fluid in sarcoidosis. Lung. 2010, 188 (2): 151-157. 10.1007/s00408-009-9218-7.CrossRefPubMed
20.
go back to reference Ishikawa N, Mazur W, Toljamo T, Vuopala K, Ronty M, Horimasu Y, Kohno N, Kinnula VL: Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma. BMC Pulm Med. 2011, 11: 22-10.1186/1471-2466-11-22.CrossRefPubMedPubMedCentral Ishikawa N, Mazur W, Toljamo T, Vuopala K, Ronty M, Horimasu Y, Kohno N, Kinnula VL: Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma. BMC Pulm Med. 2011, 11: 22-10.1186/1471-2466-11-22.CrossRefPubMedPubMedCentral
21.
go back to reference Inoue Y, Barker E, Daniloff E, Kohno N, Hiwada K, Newman LS: Pulmonary epithelial cell injury and alveolar-capillary permeability in berylliosis. Am J Respir Crit Care Med. 1997, 156 (1): 109-115.CrossRefPubMed Inoue Y, Barker E, Daniloff E, Kohno N, Hiwada K, Newman LS: Pulmonary epithelial cell injury and alveolar-capillary permeability in berylliosis. Am J Respir Crit Care Med. 1997, 156 (1): 109-115.CrossRefPubMed
22.
go back to reference Abe M, Kufe D: Structural analysis of the DF3 human breast carcinoma-associated protein. Cancer Res. 1989, 49 (11): 2834-2839.PubMed Abe M, Kufe D: Structural analysis of the DF3 human breast carcinoma-associated protein. Cancer Res. 1989, 49 (11): 2834-2839.PubMed
23.
go back to reference listed. Na Suppl 1: Proceedings of the International Society for Oncodevelopmental Biology and Medicine (ISOBM) TD-4 International Workshop on Monoclonal Antibodies against MUC1. San Diego, California, November 17–23, 1996. Tumour Biol. 1998, 19: 1-152. listed. Na Suppl 1: Proceedings of the International Society for Oncodevelopmental Biology and Medicine (ISOBM) TD-4 International Workshop on Monoclonal Antibodies against MUC1. San Diego, California, November 17–23, 1996. Tumour Biol. 1998, 19: 1-152.
24.
go back to reference Vinall LE, Pratt WS, Swallow DM: Detection of mucin gene polymorphism. Methods Mol Biol. 2000, 125: 337-350.PubMed Vinall LE, Pratt WS, Swallow DM: Detection of mucin gene polymorphism. Methods Mol Biol. 2000, 125: 337-350.PubMed
25.
go back to reference Eklund A, Blaschke E: Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis. Thorax. 1986, 41 (8): 629-634. 10.1136/thx.41.8.629.CrossRefPubMedPubMedCentral Eklund A, Blaschke E: Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis. Thorax. 1986, 41 (8): 629-634. 10.1136/thx.41.8.629.CrossRefPubMedPubMedCentral
26.
go back to reference Hermans C, Bernard A: Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med. 1999, 159 (2): 646-678.CrossRefPubMed Hermans C, Bernard A: Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med. 1999, 159 (2): 646-678.CrossRefPubMed
27.
go back to reference Taylor AE, Gaar KA: Estimation of equivalent pore radii of pulmonary capillary and alveolar membranes. Am J Physiol. 1970, 218 (4): 1133-1140.PubMed Taylor AE, Gaar KA: Estimation of equivalent pore radii of pulmonary capillary and alveolar membranes. Am J Physiol. 1970, 218 (4): 1133-1140.PubMed
28.
go back to reference Conhaim RL, Eaton A, Staub NC, Heath TD: Equivalent pore estimate for the alveolar-airway barrier in isolated dog lung. J Appl Physiol. 1988, 64 (3): 1134-1142.PubMed Conhaim RL, Eaton A, Staub NC, Heath TD: Equivalent pore estimate for the alveolar-airway barrier in isolated dog lung. J Appl Physiol. 1988, 64 (3): 1134-1142.PubMed
29.
go back to reference Swanson JA, Kern DF: Characterization of pulmonary endothelial charge barrier. Am J Physiol. 1994, 266 (4 Pt 2): H1300-H1303.PubMed Swanson JA, Kern DF: Characterization of pulmonary endothelial charge barrier. Am J Physiol. 1994, 266 (4 Pt 2): H1300-H1303.PubMed
30.
go back to reference Lai-Fook SJ, Brown LV: Effects of electric charge on hydraulic conductivity of pulmonary interstitium. J Appl Physiol. 1991, 70 (5): 1928-1932.PubMed Lai-Fook SJ, Brown LV: Effects of electric charge on hydraulic conductivity of pulmonary interstitium. J Appl Physiol. 1991, 70 (5): 1928-1932.PubMed
31.
go back to reference Noel-Georis I, Bernard A, Falmagne P, Wattiez R: Database of bronchoalveolar lavage fluid proteins. J Chromatogr B Analyt Technol Biomed Life Sci. 2002, 771 (1–2): 221-236.CrossRefPubMed Noel-Georis I, Bernard A, Falmagne P, Wattiez R: Database of bronchoalveolar lavage fluid proteins. J Chromatogr B Analyt Technol Biomed Life Sci. 2002, 771 (1–2): 221-236.CrossRefPubMed
32.
go back to reference Hilkens J, Buijs F: Biosynthesis of MAM-6, an epithelial sialomucin. Evidence for involvement of a rare proteolytic cleavage step in the endoplasmic reticulum. J Biol Chem. 1988, 263 (9): 4215-4222.PubMed Hilkens J, Buijs F: Biosynthesis of MAM-6, an epithelial sialomucin. Evidence for involvement of a rare proteolytic cleavage step in the endoplasmic reticulum. J Biol Chem. 1988, 263 (9): 4215-4222.PubMed
33.
go back to reference listed Na: NIH conference. Pulmonary sarcoidosis: a disease characterized and perpetuated by activated lung T-lymphocytes. Ann Intern Med. 1981, 94 (1): 73-94.CrossRef listed Na: NIH conference. Pulmonary sarcoidosis: a disease characterized and perpetuated by activated lung T-lymphocytes. Ann Intern Med. 1981, 94 (1): 73-94.CrossRef
34.
go back to reference Drent M, van Velzen-Blad H, Diamant M, Hoogsteden HC, van den Bosch JM: Relationship between presentation of sarcoidosis and T lymphocyte profile. A study in bronchoalveolar lavage fluid. Chest. 1993, 104 (3): 795-800. 10.1378/chest.104.3.795.CrossRefPubMed Drent M, van Velzen-Blad H, Diamant M, Hoogsteden HC, van den Bosch JM: Relationship between presentation of sarcoidosis and T lymphocyte profile. A study in bronchoalveolar lavage fluid. Chest. 1993, 104 (3): 795-800. 10.1378/chest.104.3.795.CrossRefPubMed
35.
go back to reference Grutters JC, Fellrath JM, Mulder L, Janssen R, van den Bosch JM, van Velzen-Blad H: Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation. Chest. 2003, 124 (1): 186-195. 10.1378/chest.124.1.186.CrossRefPubMed Grutters JC, Fellrath JM, Mulder L, Janssen R, van den Bosch JM, van Velzen-Blad H: Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation. Chest. 2003, 124 (1): 186-195. 10.1378/chest.124.1.186.CrossRefPubMed
36.
go back to reference Jones JG, Minty BD, Lawler P, Hulands G, Crawley JC, Veall N: Increased alveolar epithelial permeability in cigarette smokers. Lancet. 1980, 1 (8159): 66-68.CrossRefPubMed Jones JG, Minty BD, Lawler P, Hulands G, Crawley JC, Veall N: Increased alveolar epithelial permeability in cigarette smokers. Lancet. 1980, 1 (8159): 66-68.CrossRefPubMed
37.
go back to reference Rusznak C, Mills PR, Devalia JL, Sapsford RJ, Davies RJ, Lozewicz S: Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2000, 23 (4): 530-536.CrossRefPubMed Rusznak C, Mills PR, Devalia JL, Sapsford RJ, Davies RJ, Lozewicz S: Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2000, 23 (4): 530-536.CrossRefPubMed
38.
go back to reference Olivera DS, Boggs SE, Beenhouwer C, Aden J, Knall C: Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro. Inhal Toxicol. 2007, 19 (1): 13-22. 10.1080/08958370600985768.CrossRefPubMed Olivera DS, Boggs SE, Beenhouwer C, Aden J, Knall C: Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro. Inhal Toxicol. 2007, 19 (1): 13-22. 10.1080/08958370600985768.CrossRefPubMed
39.
go back to reference Honda Y, Kuroki Y, Matsuura E, Nagae H, Takahashi H, Akino T, Abe S: Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med. 1995, 152 (6 Pt 1): 1860-1866.CrossRefPubMed Honda Y, Kuroki Y, Matsuura E, Nagae H, Takahashi H, Akino T, Abe S: Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med. 1995, 152 (6 Pt 1): 1860-1866.CrossRefPubMed
40.
go back to reference Leth-Larsen R, Garred P, Jensenius H, Meschi J, Hartshorn K, Madsen J, Tornoe I, Madsen HO, Sorensen G, Crouch E: A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol. 2005, 174 (3): 1532-1538.CrossRefPubMed Leth-Larsen R, Garred P, Jensenius H, Meschi J, Hartshorn K, Madsen J, Tornoe I, Madsen HO, Sorensen G, Crouch E: A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol. 2005, 174 (3): 1532-1538.CrossRefPubMed
Metadata
Title
Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis
Authors
Masahiko Shigemura
Yasuyuki Nasuhara
Satoshi Konno
Chikara Shimizu
Kazuhiko Matsuno
Etsuro Yamaguchi
Masaharu Nishimura
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-111

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