Distribution and levels of alpha‐1‐antitrypsin in the lung and plasma in smokers and chronic obstructive pulmonary disease

Abstract

Our recent non‐biased proteomic screening study revealed elevated SerpinA1 i.e. alpha‐1‐antitrypsin (AAT) levels in induced sputum of smokers with Chronic obstructive pulmonary disease (COPD). This study was designed to further investigate the role of AAT in smokers and subjects with COPD. The expression/distribution of AAT was studied by immunohistochemistry/digital image morphometry in the lung, by Western blot in the lung and sputum, and by ELISA in the plasma at baseline (n = 349) and after a 2‐year follow‐up (n = 58). AAT was localized mainly in airway and alveolar epithelium and endothelium, especially in smokers and in those with COPD. AAT was elevated in smokers and in subjects with COPD in the lung endothelial cells. Total lung AAT immunoreactivity was elevated in subjects with moderate COPD compared with smokers and with non‐smokers. AAT showed elevated tendency in sputum of smokers with COPD compared with ‘healthy’ smokers. Plasma AAT levels were elevated in smokers with/without COPD compared with non‐smokers. In the follow‐up, plasma AAT concentrations decreased significantly after quitting smoking. Chronic smoking/COPD leads to AAT elevation especially in the endothelium of the lung periphery; these changes reflect only modestly to the AAT in sputum, while plasma AAT significantly reflects smoking‐related systemic manifestations, and decreases after smoking cessation.

Activity ofα1-Antitrypsin and Some Lysosomal Enzymes in the Blood Serum of Patients with Chronic Obstructive Pulmonary Disease after Smoking Cessation

“…Serapinas et al [ 20 ] demonstrated that the increase in the AAT concentration in blood serum is related to smoking, as they observed a higher concentration of this enzyme in current smokers and exsmokers than in never-smokers. Higher level of AAT in the blood serum of smokers was also demonstrated by Linja-Aho et al [ 10 ]. The concentration of AAT was higher in smokers without COPD and in smokers with COPD than in healthy nonsmokers.…”

“…AAT is a protein belonging to serine protease inhibitors. It is synthesized mainly in the liver and belongs to the acute phase plasma proteins associated with acute inflammatory episodes including infectious and obstructive lung diseases [ 10 ]. It is hypothesized that plasma AAT may be a noninvasive marker of smoking-related inflammation or COPD [ 10 ].…”

“…It is synthesized mainly in the liver and belongs to the acute phase plasma proteins associated with acute inflammatory episodes including infectious and obstructive lung diseases [ 10 ]. It is hypothesized that plasma AAT may be a noninvasive marker of smoking-related inflammation or COPD [ 10 ]. Among the cell organelles playing the key role at many stages of the inflammatory process are lysosomes [ 11 ].…”

The human placental proteome is affected by maternal smoking

“…This is due to the differences in risk factors for pregnancy: SERPINA1 was increased in placentas of obese mothers [26] and decreased in preeclamptic mothers [27]. SERPINA1 is increased in the lung and sputum of smokers [28], which, together with our data and known effects of smoking on the placenta [29], suggests that specific SERPINA1 isoforms could serve as a biomarker for oxidative stress. It is also possible that the alterations in placental SERPINA1 expression levels reflect responses to external stress factors and, therefore, could reflect the overall maturation process or well-being of the foeto-placental unit.…”

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

“…Deficiency of α-1-antitrypsin, encoded by Serpina1s, renders the organism vulnerable to breakdown by neutrophil elastases and the deficiency has been correlated to chronic obstructive pulmonary disease (COPD) (Chappell et al, 2006;Dahl et al, 2002;Kueppers et al, 1969). In addition, studies have shown a correlation between cigarette smoking and increased levels of α-1-antitrypsin in the lungs (Linja-Aho et al, 2013;Olsen et al, 1975). The observed differential expression of Serpina1s in the present study may indicate that CNT Large exposure could be a risk factor for COPD in a similar fashion to cigarette smoke.…”