α1 antitrypsin
Prolastin, a pharmaceutical preparation of purified human α1-antitrypsin, blocks endotoxin-mediated cytokine release
... α1-antitrypsin (AAT) is a glycoprotein, which is the major inhibitor of neutrophil elastase and proteinase 3 [1,2]. AAT is mainly produced in liver cells, but also in extrahe- patic cells, such as ...
11
Liver injury in α1 antitrypsin deficiency: an aggregated protein induces mitochondrial injury
... 22. Werner, E.D., Brodsky, J.L., and McCracken, A.A. 1996. Proteasome-depend- ent endoplasmic reticulum-associated protein degradation: an unconven- tional route to a familiar fate. Proc. Natl. Acad. Sci. USA. ...
6
Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1 antitrypsin by wild type donor hepatocytes
... mutant α1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver injury and pulmonary ...
6
Characterising the association of latency with α1 antitrypsin polymerisation using a novel monoclonal antibody
... sues from proteolytic damage. The Z mutant (Glu342Lys) undergoes inactivating conformational change and polymerises. Polymers are retained within the hepatocyte endoplasmic reticulum (ER) in homozy- gous (PiZZ) ...
12
Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency
... Our study was not designed to establish a causative role of MMP-9 in antitrypsin deficient emphysema pro- gression. Evidence from other studies suggest that MMP-9 degrades basement membrane type IV collagen, ...
11
Danazol induced Augmentation of Serum α1 Antitrypsin Levels in Individuals with Marked Deficiency of this Antiprotease
... protease-antiprotease homeostasis within the lung parenchyma. Because danazol, an impeded androgen, elevates levels of C1 inhibitor in patients deficient of that serum antiprotease, we hypothesized that this agent might ...
7
Targeted screening programmes in COPD: how to identify individuals with α1-antitrypsin deficiency
... Alpha-1 Antitrypsin Network we are now accumulating rigorous epidemiological data and creating levels of expertise that will improve the identification and management of patients at high risk of developing COPD ...
6
α1 Antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
... The process of polymerization is perhaps most strik- ing in a recently described inclusion body dementia, familial encephalopathy with neuroserpin inclusion bodies (FENIB), that results from polymerization of the ...
7
Endoplasmic reticulum stress in the lung : lessons from α1-antitrypsin deficiency
... while roughly 1 in 1700 Northern Europeans are PiZZ homozygotes, which is as common as cystic fibrosis-associated CFTR mutation. Although the PiZZ homozygotes are extremely prone to develop disease (9), there is a high ...
232
Long-term experience in the treatment of α1-antitrypsin deficiency: 25 years of augmentation therapy
... Another landmark study in the area of AATD research was published by the Alpha-1-Antitrypsin Deficiency Registry Study Group [8]. In this study of 1129 individuals with severe AATD enrolled in the US National ...
6
Acute-Phase Protein α1-Antitrypsin Inhibits Neutrophil Calpain I and Induces Random Migration
... A rapid recruitment of neutrophils to sites of injury or infection is a hallmark of the inflammatory response and is required for ef- fective host defense against pathogenic stimuli. However, neutrophil-mediated ...
10
Crystallographic and cellular characterisation of two mechanisms stabilising the native fold of α1 Antitrypsin: implications for disease and drug design
... antitrypsin. In the case of the Gly117Phe mutation, the structural mechanism whereby the changes in the vicinity of the F helix may impede formation of a β- hairpin donor/acceptor M ⁎ species is less intuitive. ...
13
Effect of Recombinant α1-Antitrypsin Fc-Fused (AAT-Fc) Protein on the Inhibition of Inflammatory Cytokine Production and Streptozotocin-Induced Diabetes
... To in- vestigate the mechanism underlying AAT-Fc–mediated effects on inflamma- tion in the mouse model of STZ-induced diabetes, we examined the levels of in- flammatory cytokines in the [r] ...
7
The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-α1-antitrypsin
... antitrypsin (8). The nature of the 2-color photobleaching in this study necessitated a longer bleaching time than that used in our previous work; this accounts at least in part for the apparently disparate results ...
16
α-Linoleic Acid Enhances the Capacity of α1-Antitrypsin to Inhibit Lipopolysaccharide-Induced IL-1β in Human Blood Neutrophils
... Alpha1-antitrypsin (A1AT, SERPINA1), a major circulating inhibitor of neutrophil elastase (NE) and proteinase-3 (PR3), has been proposed to reduce the processing and release of IL-1β. Since the antiinflammatory ...
14
α1-antitrypsin mitigates NLRP3-inflammasome activation in amyloid β1–42-stimulated murine astrocytes
... A1AT: α 1-antitrypsin; AD: Alzheimer ’ s disease; ASC: Apoptosis-associated speck-like protein containing a CARD; A β : Amyloid β ; CARD: Caspase activation and recruitment domain; Casp1: Caspase 1; CNS: Central ...
15
Fecal α1-Antitrypsin and Hemoglobin Excretion in Healthy Human Milk-, Formula-, or Cow's Milk-Fed Infants
... In later studies performed by Wilson et al,6 both guaiac-positive stools and abnormal fecal 51Cr-labeled RBC loss were induced by feeding fresh whole cow’s milk to infants who had previo[r] ...
10
The association between adiponectin, HDL-cholesterol and α1-antitrypsin-LDL in female subjects without metabolic syndrome
... While a1-antitrypsin (AT), a serine-proteinase inhibi- tor, protects tissues from damage caused by excess activities of proteinases [16], when AT is oxidized, it loses its inhibitory activity and activates ...
5
α1-antitrypsin promotes SPLUNC1-mediated lung defense against Pseudomonas aeruginosa infection in mice
... Background: Pseudomonas aeruginosa (PA) infection is involved in various lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. However, treatment of PA infection is not very effective in part ...
7
Heteropolymerization of S, I, and Z α1 antitrypsin and liver cirrhosis
... mixed together in equal amounts at 41°C and 2 mg/ml for 14 days, and in all cases resulted in the formation of polymers as assessed by nondenaturing PAGE (Figure 6a). Excitation of the resulting mixed incubation at 492 ...
9