IngentaConnect Regulation of Hemostasis by Singlet-Oxygen (1DeltaO2)

Author: Thomas W. Stief¹

Source: Current Vascular Pharmacology, Volume 2, Number 4, October 2004 , pp. 357-362(6)

Publisher: Bentham Science Publishers

Abstract:

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 Dgr

O2 *). Physiologically, 1 Dgr

O2 * 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 Dgr

O2 * inactivates the factors I (fibrinogen), V, VIII, vWF, X, plasminogen activator inhibitor-1 (PAI-1), and 1 Dgr

O2 * oxidation of plasminogen and fibrin facilitates their specific cleavage by plasminogen activators and plasmin. Furthermore, 1 Dgr

O2 * downregulates thrombocyte-function and upregulates PMNfunction. Chloramines seem to be the main physiologic generators of 1 Dgr

O2 * : in concentrations of 0.1-2 mM in blood they strongly inhibit coagulation and enhance thrombolysis. The biogenesis and reaction pattern of 1 Dgr

O2 * is of importance to understand the PMN-physiology in hemostasis, giving rise to new therapy forms of thromboatherothrombosis in man.

Keywords: Singlet-Oxygen; hemostasis; thrombi; polymorphonuclear granulocytes; thrombolysis; nonradical excited oxidant; singlet molecular oxygen

Document Type: Review article

DOI: 10.2174/1570161043385420

Affiliations: 1: Department of Clinical Chemistry, Philipps-University Hospital, D-35033 Marburg, Germany.

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Regulation of Hemostasis by Singlet-Oxygen (1O2*)