Anti-proteaasi-proteaasi tasapaino hengitysteissä

Esimerkkinä kystinen fibroosi:

https://www.researchgate.net/figure/The-importance-of-the-balance-between-proteases-and-antiproteases-in-CF-airways-The_fig1_44579199

The main source of protease activity in the CF lung is thought to be activated neutrophils, however, the role of proteases derived from other cell sources, such as mononuclear and epithelial cells, as well as exogenously derived bacterial proteases may also play a vital role in mediating destruction of the lung as seen in CF (as illustrated in Fig. 1). The main emphasis of this review will be to address the role of these endogenous and exogenous proteases and describe past, present and future developments in the search for an efficient antiprotease therapy in CF.

https://www.researchgate.net/profile/Cliff_Taggart/publication/44579199/figure/fig1/AS:203132643614727@1425442004177/The-importance-of-the-balance-between-proteases-and-antiproteases-in-CF-airways-The.png




The release of proteolytic enzymes during the inflammatory response has enormous potential to exacerbate and prolong inflammation causing numerous deleterious effects such as lung tissue destruction and reduced bacterial clearance.

To counteract this, the airways are equipped with a highly regulated antiprotease shield to dampen and control excessive proteolytic activity. The protease-antiprotease imbalance hypothesis of chronic neutrophil-mediated lung disease contends that this imbalance, or overwhelming of the natural antiprotease defence mechanisms, determines pulmonary phenotype [31].

 Several CF studies have correlated protease lung burden with disease severity and have shown an inverse relationship to the status of the antiprotease defence shield [7, 32-34].

The function of the airway antiprotease defence system is to inhibit the activity of cognate proteases thereby preventing potentially damaging degradation of host tissue (Fig. 1).

The primary antiproteases of the airway are AAT, secretory leucoprotease inhibitor (SLPI), elafin, TIMPs and cystatins [31, 35-38]. The primary protease targets of AAT, SLPI and elafin are the serine proteases, NE, proteinase 3 and cathepsin G, all of which are released by activated neutrophils [30, 31, 35, 36].