Member and Head
Coagulation Biology Laboratory
Oklahoma Medical Research Foundation
Natural anticoagulant/anti-inflammatory mechanisms
1Coagulation Biology Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
Activated protein C has been shown to reduce complications in a variety of disease models including sepsis, diabetes, inflammatory bowel disease, asthma and stroke. Thrombomodulin is involved not only in protein C activation but in down regulating complement activation. Mutations in thrombomodulin have been identified that eliminate its ability to inhibit complement activation. Patients with these mutations appear to be susceptible to atypical hemolytic uremic syndrome, the onset of which is often linked to some inflammatory stimulus. The endothelial protein C receptor (EPCR) is involved in binding protein C and increasing protein C activation rates. It also binds activated protein C and that complex enhances endothelial barrier function and decreases elaboration of adhesion molecules on endothelium, processes that involve activation of protease activated receptors. EPCR also serves as a binding site for malaria infected red cells. This interaction appears to contribute to stroke in infected children. In many inflammatory diseases, cells release DNA histone complexes. The histones activate toll like receptors 2, 4 and 9 thereby triggering an inflammatory response. The histones contribute to organ transplant injury, acetaminophen toxicity, sepsis, lung injury, radiation injury, ischemic stroke and most likely trauma induced organ injury. Activated protein C can cleave the most active histones and thereby block their pro-inflammatory activity. Thus, the pathway serves many functions in modulating inflammatory diseases.
09:00 - 10:30
|Controlling Inflammation & Coagulation||Natural anticoagulant/anti-inflammatory mechanisms||Plenary Room 1|