The Role of Serine Proteases and Antiproteases in the Cystic Fibrosis Lung

TL;DR

This paper explores how imbalanced protease and antiprotease levels in cystic fibrosis patients contribute to lung disease and inflammation.

Contribution

The study highlights the role of antiproteases as potential therapeutic targets for cystic fibrosis lung disease.

Findings

CF lungs have elevated neutrophil serine proteases that disrupt homeostasis.

Protease/antiprotease imbalance leads to impaired mucus clearance and inflammation.

Antiproteases are being explored as possible treatments for CF lung disease.

Abstract

Cystic fibrosis (CF) lung disease is an inherited condition with an incidence rate of approximately 1 in 2500 new born babies. CF is characterized as chronic infection of the lung which leads to inflammation of the airway. Sputum from CF patients contains elevated levels of neutrophils and subsequently elevated levels of neutrophil serine proteases. In a healthy individual these proteases aid in the phagocytic process by degrading microbial peptides and are kept in homeostatic balance by cognate antiproteases. Due to the heavy neutrophil burden associated with CF the high concentration of neutrophil derived proteases overwhelms cognate antiproteases. The general effects of this protease/antiprotease imbalance are impaired mucus clearance, increased and self-perpetuating inflammation, and impaired immune responses and tissue. To restore this balance antiproteases have been suggested as potential therapeutics or therapeutic targets. As such a number of both endogenous and synthetic antiproteases have been trialed with mixed success as therapeutics for CF lung disease.

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