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.
Stief
Thomas W
TW
Department of Clinical Chemistry, Philipps-University Hospital, D-35033 Marburg, Germany. thstief@med.uni-marburg.de
D000818:Animals; D005342:Fibrinolysis / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism; D016877:Oxidants / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D026082:Singlet Oxygen / Q000502:physiology*; D013927:Thrombosis / Q000097:blood*
D016877:Oxidants; D026082:Singlet Oxygen; D010100:Oxygen