Cathepsin G, a regulator of human vitamin K, dependent clotting factors and inhibitors

Acquired Isolated Factor VII Deficiency during Sepsis

“…So it can be suggested that HLE and cathepsin G released from activated granulo cytes may be partly responsible for the low level of FVII that has been observed in sepsis. Whether cathepsin G can affect the clotting activity of FVII in plasma remains controver sial: degradation of human FX or FVII by cathepsin G has been reported by some au thors while others could not confirm these findings [28], Actually, in vivo, cathepsin G is neutralised by antiprotease activity of circu lating blood [29], Yet, some reports have focused on the persistence of HLE and ca thepsin G proteolytic activities when associat ed with cell surfaces [30][31][32], Both PMN and monocytes are able to bind HLE and cathepsin G [33], Monocytes stimulated by endotox ins, complement components or tumor necro sis factor express TF [34], TF binds to FVII leading to coagulation activation. The prox imity of FVII linked to TF and cathepsin G or HLE may favour the enzymatic degradation of FVII on the cell surface.…”

Measurement of free and membrane-bound cathepsin G in human neutrophils using new sensitive fluorogenic substrates

“…All can participate, for example, in connective tissue degradation (reviewed in [5]), regulation of cytokine bioactivity [6] and inhibition of thrombin-induced cell activation [7], but the contribution of cathepsin G is uncertain. Cathepsin G also participates in a variety of other functions including platelet activation [8], proteolysis of blood coagulation factors [9], angiotensin II generation [10], chemotactic activity on monocytes [11], and anti-fungal [12] and bactericidal [13] activity. It also increases the susceptibility of monocytes\macrophages to acute HIV-1 infection [14] and activates progelatinase B in itro more efficiently than HNE or Pr3 [15].…”

Cathepsin G Inactivates Human Protein S in vitro

“…The cleavage of the Phe: Tyr bond is typical of the specificity of cathepsin G [21] but is different from that observed in other vitamin K-dependent zy mogens [8][9][10][11] (fig. 5).…”

“…5. Diagram comparing the site cleaved in protein S by cathepsin G to that in factor II [8], factor VII [ 11 ], factor IX [11], factor X [9] and protein C [ 10).…”

“…Cathepsin G (EC 3.4.21.20) has been shown to remove the calcium-binding region of five vitamin K-dependent zymogens by selective cleavage [8][9][10][11]. Since protein S is also vitamin K dependent we wondered if cathepsin G had any effect on its anticoagu lant activity and by what mode of action the activity was removed.…”