Proteomics of Human Lung Tissue Identifies Surfactant Protein A as a Marker of Chronic Obstructive Pulmonary Disease

Ohlmeier, Steffen; Vuolanto, Minna; Toljamo, Tuula; Vuopala, Katri; Salmenkivi, Kaisa; Myllärniemi, Marjukka; Kinnula, Vuokko L.

doi:10.1021/pr800423x

Cited by 85 publications

(77 citation statements)

References 47 publications

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“…Detailed cell profiles were assessed for all sputum samples. Since SP-A is expressed in alveolar epithelium and bronchial epithelial cells of smokers [26], and in the tracheal epithelial cells [35], all samples, i.e. also those containing epithelial cells, were included in the analyses.…”

Section: Study Subjectsmentioning

confidence: 99%

“…Induced sputum is virtually a noninvasive, safe and rather reproducible sampling technique, which is in widespread use in studies on chronic airway diseases [23][24][25], but there is very little data on SP-A levels in induced sputum. Our recent non-hypothesis driven proteomic studies on lung tissues revealed a remarkable elevation of SP-A in the lung tissues of COPD patients, even in the earlier stages of the disease [26]. Based on these observations together with the results from the large study of KOBAYASHI et al [9], it was hypothesised that plasma and sputum (a sample that derives directly from the lung), SP-A may be considered as an early marker for lung stress reaction/minimal lung injury in smokers, even before any decline of lung function has occurred.…”

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confidence: 91%

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Elevation of surfactant protein A in plasma and sputum in cigarette smokers

Mazur¹,

Toljamo²,

Ohlmeier³

et al. 2011

Eur Respir J

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Serum surfactant protein (SP)-A has been postulated to associate with pulmonary fibrosis, but its role in cigarette smoking-related lung diseases is undefined.SP-A levels in plasma and induced sputum in nonsmokers, smokers with respiratory symptoms (cough and/or phlegm) and symptom-free smokers were assessed using a validated EIA method. A total of 474 current smokers without any diseases or medications were enrolled and followed for 2 yrs with 111 of them succeeding in stopping.Plasma SP-A level was detectable in all subjects and elevated in smokers independently of the symptoms compared to nonsmokers (p50.001). After 2 yrs of follow-up, the SP-A level was higher in those who continued smoking compared to the quitters (p,0.001). Plasma SP-A levels were associated with age, smoking history and lung function. Sputum (n5109) SP-A was nondetectable in most nonsmokers, whereas smoking and symptoms increased sputum SP-A highly significantly (p50.001).In conclusion, SP-A may be involved in pathogenesis of cigarette smoking-related lung diseases. Further studies are needed to elucidate the role of SP-A in chronic obstructive pulmonary disease.

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Section: Study Subjectsmentioning

confidence: 99%

mentioning

confidence: 91%

Elevation of surfactant protein A in plasma and sputum in cigarette smokers

Mazur¹,

Toljamo²,

Ohlmeier³

et al. 2011

Eur Respir J

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“…Two of the biomarkers studied here are previously well-characterised neutrophil-derived inflammatory molecules, myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL), both of which are associated with inflammation and early airway injury in smokingrelated diseases [8]. Recently using two-dimensional electrophoresis and mass spectrometry we have shown that surfactant protein A (SP-A), which has multiple immunomodulatory roles in lung host defence, is associated with cigarette smoke-induced lung injury and in the development of COPD [9][10][11]. The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor abundantly expressed in type I pneumocytes.…”

Section: Introductionmentioning

confidence: 99%

Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap

et al. 2013

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The pathophysiological features of chronic obstructive pulmonary disease (COPD)-asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells.Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n526), smokers (n523), asthma (n532), COPD (n539) and COPD-asthma overlap patients (n514).In patients with COPD-asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD-asthma overlap compared with COPD (p50.00016) and could be used to differentiate patients with overlap from those with COPD.Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD-asthma overlap. @ERSpublications Increased sputum levels of neutrophil gelatinase-associated lipocalin in COPD-asthma overlap versus COPD/asthma patients

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“…Proteomics is a nonbiased screening technique that has been used to investigate various sample types including bronchoalveolar lavage fluid (BALF) (21,28,36), induced sputum (10,14,23,24), and lung tissue (17,26) to identify novel markers for COPD. In recent proteomic studies from our laboratory the major findings included an elevation of surfactant protein-A (SP-A) and a decrease of specific variants of the receptor for advanced glycation end products (RAGE) in lung tissue (25,26) and polymeric immunoglobulin receptor in sputum samples from patients with COPD (24).…”

mentioning

confidence: 99%

“…In recent proteomic studies from our laboratory the major findings included an elevation of surfactant protein-A (SP-A) and a decrease of specific variants of the receptor for advanced glycation end products (RAGE) in lung tissue (25,26) and polymeric immunoglobulin receptor in sputum samples from patients with COPD (24). Of these, SP-A and soluble RAGE have been validated in longitudinal approaches in larger cohorts (16,20).…”

mentioning

confidence: 99%

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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-A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing foldcontaining protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n ϭ 31), smokers (n ϭ 169), and patients with COPD (n ϭ 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV 1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smokingrelated lung diseases.

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Proteomics of Human Lung Tissue Identifies Surfactant Protein A as a Marker of Chronic Obstructive Pulmonary Disease

Cited by 85 publications

References 47 publications

Elevation of surfactant protein A in plasma and sputum in cigarette smokers

Elevation of surfactant protein A in plasma and sputum in cigarette smokers

Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

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