A5016435467- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Antimicrobial Peptides and Activities
- Pancreatic function and diabetes
- Heme Oxygenase-1 and Carbon Monoxide
- Machine Learning in Bioinformatics
- Peroxisome Proliferator-Activated Receptors
- Chemokine receptors and signaling
- Clusterin in disease pathology
- Metabolism and Genetic Disorders
- Glycosylation and Glycoproteins Research
- S100 Proteins and Annexins
- Hemoglobin structure and function
- Advancements in Transdermal Drug Delivery
- Sepsis Diagnosis and Treatment
- Protein Hydrolysis and Bioactive Peptides
- Natural product bioactivities and synthesis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Biochemical and Structural Characterization
- RNA Interference and Gene Delivery
- Amoebic Infections and Treatments
- Advanced Biosensing Techniques and Applications
- Neonatal Health and Biochemistry
- SARS-CoV-2 and COVID-19 Research
German Center for Lung Research
2017-2024
Medizinische Hochschule Hannover
2017-2024
Clinica de Pneumologie Iaşi
2021
Heme is a ubiquitous compound of human tissues, and it involved in cellular physiology metabolism. Once released from the cell, free heme oxidizes to ferric state (hemin). High levels hemin can cause oxidative stress inflammation if not neutralized immediately by specialized scavenger proteins. Human alpha1-antitrypsin (A1AT), an acute-phase glycoprotein important inhibitor neutrophil proteases, also hemin-binding protein. A short-term exposure freshly isolated blood neutrophils 4 µM results...
Alpha-1 antitrypsin (AAT) is a major inhibitor of serine proteases in mammals. Therefore, its deficiency leads to protease-antiprotease imbalance and risk for developing lung emphysema. Although therapy with human plasma-purified AAT attenuates deficiency-related emphysema, impact on antibacterial immunity poorly defined. Here, we examined the effect protective AAT-deficient (KO) mice challenged Streptococcus pneumoniae. AAT-KO were highly susceptible S. pneumoniae, as determined by severe...
Abstract Elevated levels of plasma alpha1-antitrypsin (AAT) correlate with a poor prognosis various cancers. Herein, we investigated effects exogenous AAT on non-small lung cancer cell lines high (H1975) and very low (H661) baseline expression SERPINA1 gene encoding protein. Comparison cells grown for 3 weeks in regular medium versus supplemented 2 mg/ml revealed that the presence acquire better proliferative properties, resistance to staurosporine (STS)-induced apoptosis, show higher CLU ,...
For the treatment of severe COVID-19, supplementation with human plasma-purified α-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory immunomodulatory activities. Researchers have demonstrated an interaction between SARS-CoV-2 spike protein (S) lipopolysaccharides (LPS) enhances pro-inflammatory responses in vitro vivo. Hence, we wanted understand potential activities plasma-derived...
Background Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology multi-organ dysfunction syndrome (MODS) sepsis. Alpha1-antitrypsin (AAT), acute phase protein with binding capacity, is one modulators host responses to inflammation. In this study, we evaluate putative protective effect AAT against MODS mortality a mouse model polymicrobial abdominal Methods Polymicrobial sepsis was induced C57BL/6N mice by cecal ligation puncture...
Human α1-antitrypsin (AAT) is an abundant acute phase glycoprotein expressing anti-protease and immunomodulatory activities, used as a biopharmaceutical to treat patients with inherited AAT deficiency. The pleiotropic properties of provide rationale for using this therapy outside Therapy administrated intravenously, yet the alternative routes are being considered. To examine putative transepidermal application we epiCS®, 3D human epidermis equivalents reconstructed from primary epidermal...
Free heme toxicity in the vascular endothelium is critical for pathogenesis of hemolytic disorders including sickle cell disease. In current study, it demonstrated that human alpha1-antitrypsin (A1AT), a serine protease inhibitor with high binding-affinity heme, rescues endothelial (EC) injury caused by free heme. A1AT provided protection against via pathway differs from serum albumin and hemopexin, two prototypical heme-binding proteins. inhibited heme-mediated pro-inflammatory activation...
The SERPINA1 gene encodes alpha1-antitrypsin (AAT), an acute phase glycoprotein and serine protease inhibitor that is mainly (80–90%) produced in the liver. Point mutations can lead to misfolding, intracellular accumulation, deficiency of circulating AAT protein, increasing risk developing chronic liver diseases or obstructive pulmonary disease. Currently, siRNA technology knock down limit defective production. How this latter affects other genes unknown. Livers were taken from age-...
Expression levels of CX3CR1 (C-X3-C motif chemokine receptor 1) on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated the regulation its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host's misfolded proteins occurring forms polymers or amyloid fibrils can regulate expression. Herein, a novel example demonstrates human ZZ alpha-1...
Human alpha-1-antitrypsin (AAT) encoded by the SERPINA1 gene, is an acute phase glycoprotein that regulates inflammatory responses via both protease inhibitory and non-inhibitory activities. We previously reported AAT controls ATP-induced IL-1β release from human mononuclear cells stimulating of small bioactive molecules. In current study, we aimed to elucidate identity these putative effectors released PBMCs in response AAT, which may inhibit LPS-induced IL-1β. pre-incubated alone or with...
Nowadays laparoscopic interventions enable the collection of resident macrophage populations out human cavities. We employed this technique to isolate pleural monocytes/macrophages from healthy young adults who underwent a correction pectus excavatum. High quality CD14+ (plMo/Mφ) were used for RNA-sequencing (RNA-seq) in comparison with monocyte-derived macrophages (MDM) natural (MDM-0) or IL-4-polarized (MDM-IL4). Transcriptome analysis revealed 7166 and 7076 differentially expressed genes...
The spectrum of haematologic disorders after lung transplantation includes inflammatory, immune-mediated or drug-related ethology. Under haemolytic conditions, free hemin derived from lysed red blood cells triggers vascular and organ dysfunction leading to adverse clinical effects. Hemin activates reactive oxygen species (ROS) production, leukocyte infiltration endothelial activation, amplifies systemic inflammation. There are proteins in biological fluids that sequester reduce its toxicity....
Chronic obstructive pulmonary disease (COPD) is associated with chronic neutrophilic inflammation and pathological changes in circulating levels of alpha1-antitrypsin (AAT), an inhibitor neutrophil proteases. Variants C-terminal fragments AAT have also been identified human body fluids tissues, including lungs. However, their biological role clinical relevance remain largely unknown. Originally it has thought that these are generated during unspecific cleavage by metalloproteases. The...
Abstract The CX3CR1 (chemokine (C-X3-C motif) receptor 1) expression levels on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. factors implicated the regulation of its specific ligand CX3CL1 (fractalkine) remain largely unknown. Recent studies provide evidence that host‘s misfolded proteins occurring forms polymers or amyloid fibrils can regulate expression. Herein, we present a novel example human ZZ...
Alpha-1-antitrypsin (AAT) is a protein of the SERPINA1 gene. A single amino acid mutation (Lys342Glu) results in an expression misfolded Z-AAT having high propensity to intra- and extra-cellular polymerization. Here we asked whether levels circulating polymers are associated with severity lung and/or liver disease. We obtained cross sectional data from Dutch part Alpha1 International Registry 52 ZZ-AAT patients who performed pulmonary function test donated blood sample on same day. From...
The C-terminal-fragments of alpha1-antitrypsin (AAT) have been identified and their diverse biological roles reported in vitro vivo. These findings prompted us to develop a monoclonal antibody that specifically recognizes C-36 peptide (corresponding residues 359–394) resulting from the protease-associated cleavage AAT. C-36-targeting mouse Immunoglobulin M (IgM) (containing κ light chains, clone C42) was generated enzyme-linked immunosorbent assay (ELISA)-tested by Davids Biotechnologie...
C-terminal fragments of alpha1-antitrypsin (AAT) occur in human biological fluids and tissues, including normal emphysema lungs. We developed novel mouse monoclonal antibody (IgM, C42 mAb) against C-36 peptide resulting from elastase-associated cleavage AAT. addressed the usefulness mAb dot western blots, immunomicroscopy flow cytometry. According to dot-blots, detect at range 0.1-0.05 µg show no cross-reactivity with native, polymeric or oxidized full-length AAT, AAT-elastase complex...