INTRODUCTION People with α1-antitrypsin deficiency are at increased risk for the development of chronic obstructive pulmonary disease. Previous retrospective epidemiologic studies have found that exposure to occupational dust among those with α1-antitrypsin deficiency is a risk factor at the group level for poorer lung function, but on an individual clinical basis, a causal attribution can be d...

a1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoietin-like protein 4 (Angptl4) in adherent human blood monocytes and in human lung microvascular endothelial cells, providing a mechanism for the broad immune-regulatory properties of A1AT independent of its antiprotease activity. In this study, we demonstrate that A1AT (Pro-lastin), a potent inducer o...

Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1 -antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant rema...

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-ant...

BACKGROUND/AIMS Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. METHODS Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead pepti...

The process of elastin and collagen fiber destruction was presented based on the example of the changes taking place in the course of chronic obstructive pulmonary disease and primary spontaneous pneumothorax. In 1963, when analyzing patients with α1 antitrypsin deficiency, Dr Laurell and Dr Eriksson hypothesized that elastolysis plays a role in the pathogenesis of emphysema, which marked the b...

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α(1)-antitrypsin (A1AT). Pathological mutations disturb the conformation...

From experiments with purified proteins, it has been concluded that factor XIa (FXIa) is inhibited in plasma mainly by alpha 1-antitrypsin (a1AT), followed by antithrombin III (ATIII), C1-inhibitor (C1Inh), and alpha 2-antiplasmin (a2AP). However, the validity of this concept has never been studied in plasma. We established the relative contribution of different inhibitors to the inactivation o...

According to world publications, mutations in the SERPINA1 gene may be a genetic risk factor for severe chronic obstructive pulmonary disease and, consequently, rapid progression of respiratory dysfunction. This leads decrease level alpha-1-antitrypsin protein. It is inherited by autosomal recessive type, but there are registered cases codominance. In absence treatment, diseases system become a...

The serpin (serine proteinase inhibitor) superfamily includes antithrombin, α1-antitrypsin and PAI-1, which control the coagulation, inflammation and fibrinolytic pathways, respectively. Serpins have a unique method of inhibition that involves a conformational change of the protein (Huntington et al., 2000). This transition is essential for the mechanism of serpin inhibition but it renders serp...