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Open Access 01-12-2008 | Research

Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study

Authors: Michael W Sims, Ruth M Tal-Singer, Sonja Kierstein, Ali I Musani, Michael F Beers, Reynold A Panettieri, Angela Haczku

Published in: Respiratory Research | Issue 1/2008

Abstract

Background

Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.

Methods

We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.

Results

Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.

Conclusion

Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.

Workshop Report: Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2006 update) [http://www.goldcopd.org]

Ferguson JS, Voelker DR, Ufnar JA, Dawson AJ, Schlesinger LS: Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J Immunol 2002,168(3):1309–1314.CrossRefPubMed

Hartshorn KL, Crouch E, White MR, Colamussi ML, Kakkanatt A, Tauber B, Shepherd V, Sastry KN: Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Am J Physiol 1998,274(6 Pt 1):L958–69.PubMed

LeVine AM, Elliott J, Whitsett JA, Srikiatkhachorn A, Crouch E, DeSilva N, Korfhagen T: Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol 2004,31(2):193–199.CrossRefPubMed

LeVine AM, Whitsett JA, Hartshorn KL, Crouch EC, Korfhagen TR: Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. J Immunol 2001,167(10):5868–5873.CrossRefPubMed

Limper AH, Crouch EC, O'Riordan DM, Chang D, Vuk-Pavlovic Z, Standing JE, Kwon KY, Adlakha A: Surfactant protein-D modulates interaction of Pneumocystis carinii with alveolar macrophages. J Lab Clin Med 1995,126(5):416–422.PubMed

Madan T, Eggleton P, Kishore U, Strong P, Aggrawal SS, Sarma PU, Reid KB: Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages. Infect Immun 1997,65(8):3171–3179.PubMedPubMedCentral

Ofek I, Mesika A, Kalina M, Keisari Y, Podschun R, Sahly H, Chang D, McGregor D, Crouch E: Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae. Infect Immun 2001,69(1):24–33.CrossRefPubMedPubMedCentral

Restrepo CI, Dong Q, Savov J, Mariencheck WI, Wright JR: Surfactant protein D stimulates phagocytosis of Pseudomonas aeruginosa by alveolar macrophages. Am J Respir Cell Mol Biol 1999,21(5):576–585.CrossRefPubMed

10.

Clark H, Palaniyar N, Hawgood S, Reid KB: A recombinant fragment of human surfactant protein D reduces alveolar macrophage apoptosis and pro-inflammatory cytokines in mice developing pulmonary emphysema. Ann N Y Acad Sci 2003, 1010:113–116.CrossRefPubMed

11.

Vandivier RW, Ogden CA, Fadok VA, Hoffmann PR, Brown KK, Botto M, Walport MJ, Fisher JH, Henson PM, Greene KE: Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol 2002,169(7):3978–3986.CrossRefPubMed

12.

Borron PJ, Crouch EC, Lewis JF, Wright JR, Possmayer F, Fraher LJ: Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol 1998,161(9):4599–4603.PubMed

13.

Haczku A: Role and regulation of lung collectins in allergic airway sensitization. Pharmacol Ther 2006,110(1):14–34.CrossRefPubMed

14.

LeVine AM, Whitsett JA: Pulmonary collectins and innate host defense of the lung. Microbes Infect 2001,3(2):161–166.CrossRefPubMed

15.

Botas C, Poulain F, Akiyama J, Brown C, Allen L, Goerke J, Clements J, Carlson E, Gillespie AM, Epstein C, Hawgood S: Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A 1998,95(20):11869–11874.CrossRefPubMedPubMedCentral

16.

Wert SE, Yoshida M, LeVine AM, Ikegami M, Jones T, Ross GF, Fisher JH, Korfhagen TR, Whitsett JA: Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A 2000,97(11):5972–5977.CrossRefPubMedPubMedCentral

17.

Yoshida M, Whitsett JA: Alveolar macrophages and emphysema in surfactant protein-D-deficient mice. Respirology 2006, 11 Suppl:S37–40.CrossRefPubMed

18.

Atochina EN, Beers MF, Hawgood S, Poulain F, Davis C, Fusaro T, Gow AJ: Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism. Am J Respir Cell Mol Biol 2004,30(3):271–279.CrossRefPubMed

19.

Casey J, Kaplan J, Atochina-Vasserman EN, Gow AJ, Kadire H, Tomer Y, Fisher JH, Hawgood S, Savani RC, Beers MF: Alveolar surfactant protein D content modulates bleomycin-induced lung injury. Am J Respir Crit Care Med 2005,172(7):869–877.CrossRefPubMedPubMedCentral

20.

Kierstein S, Poulain FR, Cao Y, Grous M, Mathias R, Kierstein G, Beers MF, Salmon M, Panettieri RA Jr., Haczku A: Susceptibility to ozone-induced airway inflammation is associated with decreased levels of surfactant protein D. Respir Res 2006, 7:85.CrossRefPubMedPubMedCentral

21.

Betsuyaku T, Kuroki Y, Nagai K, Nasuhara Y, Nishimura M: Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid. Eur Respir J 2004,24(6):964–970.CrossRefPubMed

22.

Honda Y, Takahashi H, Kuroki Y, Akino T, Abe S: Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. Chest 1996,109(4):1006–1009.CrossRefPubMed

23.

Bates SR, Gonzales LW, Tao JQ, Rueckert P, Ballard PL, Fisher AB: Recovery of rat type II cell surfactant components during primary cell culture. Am J Physiol Lung Cell Mol Physiol 2002,282(2):L267–76.CrossRefPubMed

24.

Cao Y, Tao JQ, Bates SR, Beers MF, Haczku A: IL-4 induces production of the lung collectin surfactant protein-D. J Allergy Clin Immunol 2004,113(3):439–444.CrossRefPubMed

25.

Haczku A, Atochina EN, Tomer Y, Chen H, Scanlon ST, Russo S, Xu J, Panettieri RA Jr., Beers MF: Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice. Am J Respir Cell Mol Biol 2001,25(1):45–50.CrossRefPubMed

26.

Cuzick J: A Wilcoxon-type test for trend. Stat Med 1985,4(1):87–90.CrossRefPubMed

27.

Fisher JH, Larson J, Cool C, Dow SW: Lymphocyte activation in the lungs of SP-D null mice. Am J Respir Cell Mol Biol 2002,27(1):24–33.CrossRefPubMed

28.

Haczku A, Cao Y, Vass G, Kierstein S, Nath P, Atochina-Vasserman EN, Scanlon ST, Li L, Griswold DE, Chung KF, Poulain FR, Hawgood S, Beers MF, Crouch EC: IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. J Immunol 2006,176(6):3557–3565.CrossRefPubMed

29.

Korfhagen TR, Sheftelyevich V, Burhans MS, Bruno MD, Ross GF, Wert SE, Stahlman MT, Jobe AH, Ikegami M, Whitsett JA, Fisher JH: Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo. J Biol Chem 1998,273(43):28438–28443.CrossRefPubMed

30.

Knudsen L, Ochs M, Mackay R, Townsend P, Deb R, Muhlfeld C, Richter J, Gilbert F, Hawgood S, Reid K, Clark H: Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice. Respir Res 2007,8(1):70.CrossRefPubMedPubMedCentral

31.

Heidinger K, Konig IR, Bohnert A, Kleinsteiber A, Hilgendorff A, Gortner L, Ziegler A, Chakraborty T, Bein G: Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced. Immunogenetics 2005,57(1–2):1–7.CrossRefPubMed

32.

Guo X, Lin HM, Lin Z, Montano M, Sansores R, Wang G, DiAngelo S, Pardo A, Selman M, Floros J: Surfactant protein gene A, B, and D marker alleles in chronic obstructive pulmonary disease of a Mexican population. Eur Respir J 2001,18(3):482–490.CrossRefPubMed

33.

Deterding RR, Shimizu H, Fisher JH, Shannon JM: Regulation of surfactant protein D expression by glucocorticoids in vitro and in vivo. Am J Respir Cell Mol Biol 1994,10(1):30–37.CrossRefPubMed

34.

Mariencheck W, Crouch E: Modulation of surfactant protein D expression by glucocorticoids in fetal rat lung. Am J Respir Cell Mol Biol 1994,10(4):419–429.CrossRefPubMed

35.

Ogasawara Y, Kuroki Y, Tsuzuki A, Ueda S, Misaki H, Akino T: Pre- and postnatal stimulation of pulmonary surfactant protein D by in vivo dexamethasone treatment of rats. Life Sci 1992,50(23):1761–1767.CrossRefPubMed

36.

Dulkerian SJ, Gonzales LW, Ning Y, Ballard PL: Regulation of surfactant protein D in human fetal lung. Am J Respir Cell Mol Biol 1996,15(6):781–786.CrossRefPubMed

37.

Wade KC, Guttentag SH, Gonzales LW, Maschhoff KL, Gonzales J, Kolla V, Singhal S, Ballard PL: Gene induction during differentiation of human pulmonary type II cells in vitro. Am J Respir Cell Mol Biol 2006,34(6):727–737.CrossRefPubMedPubMedCentral

38.

Wang JY, Yeh TF, Lin YC, Miyamura K, Holmskov U, Reid KB: Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome. Thorax 1996,51(9):907–913.CrossRefPubMedPubMedCentral

Title: Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study
Authors: Michael W Sims
Ruth M Tal-Singer
Sonja Kierstein
Ali I Musani
Michael F Beers
Reynold A Panettieri
Angela Haczku
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2008
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/1465-9921-9-13

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