Regulation of hemostasis by singlet-oxygen (1DeltaO2*).

Hemostasis is the system of generation and destruction of thrombi. It consists of coagulation and thrombolysis and has a plasmatic part and a cellular one, the latter being the thrombocytes and endothelial cells for coagulation and the polymorphonuclear granulocytes (PMN) for thrombolysis. Main products of PMN are oxidants of the hypochlorite/chloramine-type that can generate the nonradical excited oxidant singlet molecular oxygen ((1)DeltaO(2)()). Physiologically, (1)DeltaO(2)() reacts with methionine and cysteine residues and with carbenic structures in lipids, generating dioxetanes, which upon disruption emit photons in the blue spectrum of light (380-450 nm). It modifies some important hemostasis components in blood: (1)DeltaO(2)() inactivates the factors I (fibrinogen), V, VIII, vWF, X, plasminogen activator inhibitor-1 (PAI-1), and alpha2-antiplasmin. (1)DeltaO(2)() oxidation of plasminogen and fibrin facilitates their specific cleavage by plasminogen activators and plasmin. Furthermore,(1)DeltaO(2)()downregulates thrombocyte-function and upregulates PMN-function. Chloramines seem to be the main physiologic generators of (1)DeltaO(2)(): in concentrations of 0.1-2 mM in blood they strongly inhibit coagulation and enhance thrombolysis. The biogenesis and reaction pattern of (1)DeltaO(2)(*) is of importance to understand the PMN-physiology in hemostasis, giving rise to new therapy forms of thromboatherothrombosis in man.