elastase

Elastase belongs to the serine protease family with a catalytic triad (His-Asp-Ser) and cleaves peptide bonds adjacent to small, nonpolar amino acids like alanine and glycine, allowing it to degrade elastin fibers. Two clinically relevant forms exist:

1. Pancreatic elastase: Secreted by pancreatic acinar cells as inactive proelastase, activated by trypsin in the duodenum. It functions in digestion of dietary proteins. Fecal elastase-1 is a clinically useful, stable marker for exocrine pancreatic insufficiency (e.g., chronic pancreatitis, cystic fibrosis) since it is not degraded during intestinal transit, unlike chymotrypsin.

2. Neutrophil elastase: Stored in azurophilic granules of neutrophils, released during inflammation to degrade bacterial virulence factors and extracellular matrix components (elastin, collagen) as part of the innate immune response. Excessive or unregulated neutrophil elastase activity is central to the pathophysiology of emphysema, particularly in alpha-1 antitrypsin (AAT) deficiency, where the lack of AAT (the primary inhibitor of neutrophil elastase) leads to unchecked elastin degradation in lung parenchyma, causing panacinar emphysema (classically affecting lower lobes). Smoking exacerbates this by increasing neutrophil recruitment and oxidatively inactivating AAT.

Clinical correlations: Low fecal elastase-1 indicates pancreatic exocrine insufficiency. Elevated neutrophil elastase activity is implicated in COPD, ARDS, and cystic fibrosis lung damage. AAT deficiency is a key genetic cause of early-onset emphysema and liver disease (due to misfolded AAT accumulation in hepatocytes), tested with serum AAT levels and genotyping (PiZZ genotype).