Lung cysteine cathepsins: intruders or unorthodox contributors to the kallikrein-kinin system?

The protease/antiprotease balance is tipped in favor of enhanced proteolysis in inflammatory lung disorders, promoting the spread and severity of inflammation. Cysteine cathepsins participate in the remodeling and/or degradation of the pulmonary extra cellular matrix and in lung homeostasis. There is now good evidence that cathepsins are involved in fibrosis, emphysema, asthma, and in bronchopulmonary dysplasia. Kinins are inflammatory mediators that induce edema, pain and vasodilatation, and participate in vascular homeostasis. Kinins may also contribute to the immune system by acting as danger signals, and activating bradykinin receptors. Kinins are believed to play a role in inflammatory obstructive airway diseases, asthma, and allergic rhinitis. Their release by plasma and tissue kallikreins is severely reduced at inflammatory sites, although local kinin production seems to remain intact. Such conflicting observations suggest that there are alternative mechanisms of kinin metabolism besides the classical pathways. This article reviews the biological and pathophysiological roles of lung cysteine cathepsins, kinins and their receptors, and summarizes the indications that cysteine cathepsins may contribute to kinin liberation and/or degradation.