Regulation of Hemostasis by Singlet-Oxygen (1ΔO2*)

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 (1ΔO2 *). Physiologically, 1ΔO2 * 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: 1ΔO2 * inactivates the factors I (fibrinogen), V, VIII, vWF, X, plasminogen activator inhibitor-1 (PAI-1), and 1ΔO2 * oxidation of plasminogen and fibrin facilitates their specific cleavage by plasminogen activators and plasmin. Furthermore, 1ΔO2 * downregulates thrombocyte-function and upregulates PMNfunction. Chloramines seem to be the main physiologic generators of 1ΔO2 * : in concentrations of 0.1-2 mM in blood they strongly inhibit coagulation and enhance thrombolysis. The biogenesis and reaction pattern of 1ΔO2 * is of importance to understand the PMN-physiology in hemostasis, giving rise to new therapy forms of thromboatherothrombosis in man.