Neutrophils generate large amounts of singlet oxygen (via NADPH-oxidase/myeloperoxidase mediated generation of chloramines).
Physiologic activation of neutrophils results in an anti-thrombotic state, probably also mediated by F13a inactivation as shown in the paper below.
Article Tytuł artykułu: Ozone-induced oxidative modification of plas...
Hi Steve,
This is a very important question. It is quite possible that singlet oxygen mediates ozone-induced inactivation of FXIII. This has some clinical implications which I will discuss below. As you know fibrinogen, FV, FVIII, FX and proteins involved in the fibrinolytic system are influenced by ROS. Although fibrinogen is more sensitive than albumin, transferrin, immunoglobulins and ceruloplasmin. It is important to determine the structural and functional properties of FXIII at different stages of its activation. It is also important to determine the structural and functional properties of FXIII at different stages of its inactivation. FXIII inactivation is very important clinically because this will enable the clot vulnerable for clot lysis. FXIII activation would result in a firmer clot and this makes the clot resistant to fibrinolysis. Optimum modulation of activation and inactivation of FXIII action to enable effective fibrinolytic action would be quite helpful in treating patients with acute myocardial infarction or thrombotic stroke who report to the hospital later than 3 hours when the FXIII is supposed to make the clot firm er and resistant to lysis.
There is probably an important role of singlet oxygen as a mediator of ozone-induced inactivation of FXIII and needs to be further explored. Steve, I hope that I have provided a clinical implications for your very important question.
Omer
High Omer,
do you think that there is a therapeutic window for treatment of Ebola-patients with singlet oxygen generators, e.g. 0.5-1 mM chloramine, a blood concentration that kills the lipid-enveloped virus but does not pathologically damage blood hemostasis ?
Maybe Ebola-patients with fresh infections could be cured by singlet oxygen.
Thomas
Hi Steve,
Hemorrhage is a major complication of Ebola virus infection. Besides the anti-viral therapy or potential vaccination against EBOLA, it is essential that you also treat the complications these patients may have. The role of singlet oxygen in the activation of FXIII may decrease the chances of hemorrhage and indirectly help the patients in coping up with this viral infection. Good thought.
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