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

Mediators Inflamm. 2015:2015:293053. doi: 10.1155/2015/293053. Epub 2015 Jun 21.

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.

Publication types

  • Review

MeSH terms

  • Cathepsin G / physiology
  • Cystic Fibrosis / metabolism*
  • Elafin / physiology
  • Humans
  • Leukocyte Elastase / physiology
  • Myeloblastin / physiology
  • Neutrophils / enzymology
  • Protease Inhibitors / metabolism*
  • Secretory Leukocyte Peptidase Inhibitor / physiology
  • Serine Proteases / physiology*
  • alpha 1-Antitrypsin / physiology

Substances

  • Elafin
  • Protease Inhibitors
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • alpha 1-Antitrypsin
  • Serine Proteases
  • Cathepsin G
  • Leukocyte Elastase
  • Myeloblastin