From clot to collagen: coagulation peptides in interstitial lung disease

The fragile architecture of the lung is constantly threatened by a barrage of insults originating from both air and blood interfaces. The necessity to protect our lungs has lead to the evolution of exquisite defence systems. These comprise a complex screen of antioxidants, a mucocilliary escalator which is constantly clearing the respiratory tract and sophisticated immune defence mechanisms. When the insult involves vascular damage, the coagulation cascade is activated and is responsible for preventing blood loss at sites of injury by promoting the generation of a fibrin clot. This is vital for haemostasis, but chronic activation of this cascade with persistent fibrin deposition is frequently observed in respiratory diseases involving both the airways (e.g. asthma, chronic obstructive pulmonary disease) and the lung parenchyma (e.g. interstitial lung disease). It is often speculated that these events might be important in the pathogenesis of these diseases, but solid evidence for this has been scarce and, until quite recently, researchers have failed to provide data which could link the features of these diseases (i.e. chronic inflammation and tissue repair) to any known actions of coagulation cascade proteins. In this article, we will review research developments which suggest an ever increasing range of cellular functions for elements of the coagulation cascade. These functions are such that many of the pro-inflammatory and fibroproliferative events which are commonly observed in respiratory diseases, and are most commonly ascribed to elements of a cytokine network, could in fact be orchestrated by proteins of the coagulation cascade. This article will focus on the relevance of these proteins in interstitial lung diseases in which tissue repair and fibrosis are commonly observed.