Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study
Open Access
- 28 January 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Respiratory Research
- Vol. 9 (1), 13
- https://doi.org/10.1186/1465-9921-9-13
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 studiedin vitrousing 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 cellsin 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.Keywords
This publication has 36 references indexed in Scilit:
- Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient miceRespiratory Research, 2007
- Role and regulation of lung collectins in allergic airway sensitizationPharmacology & Therapeutics, 2006
- Alveolar macrophages and emphysema in surfactant protein‐D‐deficient miceRespirology, 2006
- Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluidEuropean Respiratory Journal, 2004
- IL-4 induces production of the lung collectin surfactant protein-DJournal of Allergy and Clinical Immunology, 2004
- Surfactant Protein D Enhances Phagocytosis and Killing of Unencapsulated Phase Variants ofKlebsiella pneumoniaeInfection and Immunity, 2001
- Surfactant Protein-D Regulates Surfactant Phospholipid Homeostasis in VivoPublished by Elsevier BV ,1998
- Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome.Thorax, 1996
- Decreased Contents of Surfactant Proteins A and D in BAL Fluids of Healthy SmokersSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 1996
- Pre- and postnatal stimulation of pulmonary surfactant protein D by in vivo dexamethasone treatment of ratsLife Sciences, 1992