It May Be That Vitamin D Binding Protein Is More Important Than Vitamin D Itself In COVID-19 Pathology
As I have previously discussed, it has been determined that the Spike Protein damages hematopoietic stem/progenitor cells in the mechanism of pyroptosis in Nlrp3 inflammasome-dependent manner. This leads to the release of cytosol components to extracellular space and final cell lysis.
And, as in endothelial injury after hematopoietic stem cell transplant it has been shown that release of the angiopathic molecule filamentous actin from hematopoietic cells lysed during conditioning prior to stem cell transplant would be associated with clinical outcomes. Therefore, we can expect the same release of F-Actin from the Spike Protein’s lysing of hematopoietic stem cells.
Platelet activation, caused by agonists such as thrombin or by contact with the extracellular matrix, leads to platelet adhesion, aggregation, and coagulation. Activated platelets undergo shape changes, adhere, and spread at the site of injury to form a blood clot.
This platelet activation is exactly what we are seeing in COVID-19: Platelets obtained from the patients may have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, showing that the increased activation potential recommends platelet can be hyper-activated in severely ill SARS-CoV-2 cases.
I believe the lysing of hematopoietic stem/progenitor cells and the subsequent release of F-Actin is inducing a significant portion of this platelet activation.
What is most interesting is that Inhibition of actin polymerization and inhibition of dynein significantly decreased the activity of thrombin-stimulated platelets.
What does Vitamin D Binding Protein (DBP) do?
Incubation of F-actin, the filamentous form of this protein, with DBP leads to depolymerization of the former.
V itamin D-binding protein and its complex with actin is also the structural basis of the actin-scavenger system.
Levels of Vitamin D Binding Protein have been found to be intimately related to levels of Vitamin D.
I believe this mechanism needs to be fully investigated and therapeutics developed if found to be correct.
Vitamin D-binding protein (Gc-globulin) binds actin
Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity
Thrombin-induced cytoskeleton dynamics in spread human platelets observed with fast scanning ion conductance microscopy
Vitamin D Binding Protein: A Historic Overview
The Differential Diagnosis and Treatment of Thrombotic Microangiopathies
When the lectin pathway of complement is activated in HSCT, lethal threats emerge
Transplant-Associated Thrombotic Microangiopathy in Pediatric Hematopoietic Cell Transplant Recipients: A Practical Approach to Diagnosis and Management
Endothelial injury, F-actin and vitamin-D binding protein after hematopoietic stem cell transplant and association with clinical outcomeshttps://haematologica.org/article/view/9700