L59: Proteases In COPD

Question 1

Types of proteases

Answer 1

1. Endopeptidase: cleave internal bonds, specific
2. Exopeptidase: terminal amino acids, non-specific
   - Aminopeptidase
   - Carboxypeptidase

Question 2

Enzymes involved in Emphysema, Peribronchial fibrosis, Mucus hypersecretion

Answer 2

Emphysema

1. Neutrophil elastase
   - Serine proteinase (from azurophilic granules)
   - IL-8 expression
   - break down elastin, TIMP (tissue inhibitor of metalloproteinase)
   - Alpha-1 Antitrypsin Deficiency (coats lung, protecting from neutrophil elastase):
   - trapped in liver —> cause liver damage
   - unprotected lung —> lung damage
2. Matrix metalloproteinase
   - Calcium-dependent zinc-containing endopeptidase
   - MMP1, 2, 9, 12
   - Breaks down elastin, TGF-beta
   - MMP12: induced by TNF-alpha, inhibit anti-protease (for macrophage and neutrophil function)
   - loss of MMP12 also protect from peribronchial fibrosis

Peribronchial fibrosis

1. TGF-beta mediated fibroblast accumulation
   - major growth factor causing fibroblast proliferation —> fibrosis
   - TGF-beta activated by MMP2, MMP9 by cleaving

Mucus hypersecretion (neutrophil-mediated: ROS, TNF-alpha)

1. EGFR
   - stimulate mucin secretion
   - Metaplasia: instructs basal cells to differentiate into mucin containing goblet cell
   - Hyperplasia: proliferation of goblet cell