nemoci-sympt/PLICNI/alfa-1-antitrypsinova-deficience/alfa-1-antitrypsinovy-inhibitor

Zařazení

• Member of the serine protease inhibitor (serpin) superfamily of proteins [4]
• Serpin peptidase inhibitor, clade A, member 1 (SERPINA1)
• Gene that encodes the protein alpha-1 antitrypsin [1]

Anti Alveolar cell apoptosis

• May also play an important role in emphysema pathogenesis
• Alpha1-antiprotease may inhibit alveolar cell apoptosis
• Protect against emphysema in the absence of neutrophilic inflammation [4]

Antiproteázové funkce

• Protects the body from the neutrophil elastase enzyme
• Which is released from white blood cells to fight infection [1]
• Protease excess in alveoli destroys alveolar walls and causes emphysema [4]
• Can disrupt connective tissue [2]
• protein is more accurately termed alpha1-antiprotease
• Inhibition of several neutrophil-derived proteases
• Trypsin
• Elastase
• Proteinase 3
• Cathepsin G [4]
• Constitutes about 95% of all the antiprotease activity in human alveoli [4]
• Lungs have a large surface area and are continuously exposed to a high burden of airborne pathogens
• Results in a cellular immune response
• Local release of oxidants and proteases
• Alpha1-antiprotease protect the lungs from unregulated protease activity [4]
• Digestion of elastin and collagen in the alveolar walls and progressive emphysema

Hladiny

Normal concentrations of AAT ranges from

• Vary with analytical
• 80 - 220 mg/dL
• 20 - 48 micromol/L [2] 20-53 µmol/L [4]
• Typically around 1.0-2.7 g/l [2]
• Nephelometry - 150 - 350 mg/dL [4] by radial immunodiffusion [1]
• AAT level below 100 mg/dL (18.4 micromols/L)
• Should be evaluated further with isoelectric focusing or genotyping [1]

Lehké deficience

• Greater than 20 micromol/L (80 mg/dL)
• Unlikely that the patient has clinically significant AAT deficiency [1]

Deficience

• Associated with plasma AAT levels less than 35% of the average normal level [3]
• Levels greater than 11 µmol/L appear to be protective

Severe AAT deficiency

• Serum level below 11 micromols/L
• Cca 57 mg/dL by nephelometry [1]
• Emphysema develops in most (but not all) individuals with serum levels less than 9 µmol/L [4]

Produkce

• Hepatocytes synthesize alpha1-antiprotease

V seru

• After its release from the liver
• Alpha1-antiprotease circulates unbound
• Diffuses into interstitial and alveolar lining fluids