antiprotease

An antiprotease is a protein or molecule that inhibits the activity of proteolytic enzymes (proteases). Antiproteases help regulate proteolysis in tissues and body fluids to prevent excessive protein degradation and collateral tissue damage during normal turnover and inflammatory responses. They contribute to the control of inflammation, tissue remodeling, and host defense.

Key examples include serine protease inhibitors of the serpin family, such as alpha-1-antitrypsin (AAT), which primarily inhibits neutrophil elastase and other serine proteases. Other antiproteases include alpha-2-macroglobulin, a broad-spectrum inhibitor that traps proteases in a form that prevents substrate access; secretory leukocyte protease inhibitor (SLPI) and elafin, produced by mucosal and epithelial tissues, which inhibit neutrophil elastase and related proteases. Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinases (MMPs), preventing excessive degradation of the extracellular matrix. Additional inhibitors act in specific contexts, such as coagulation factors that inhibit proteases in the clotting cascade.

Physiologically, antiproteases maintain tissue integrity during inflammation by balancing protease activity released from neutrophils and other cells. A deficiency or imbalance can lead to unchecked proteolysis and tissue damage. For example, inherited alpha-1-antitrypsin deficiency is associated with early-onset emphysema and liver disease, reflecting the importance of antiprotease protection in the lungs and liver.

Clinically, antiprotease therapy includes augmentation therapy with purified AAT for deficiency and the development of synthetic or biological inhibitors aimed at reducing protease-driven tissue damage in diseases such as chronic obstructive pulmonary disease and inflammatory disorders.