Shear induced tissue factor activity in human leukocytes
Pankowsky, Dan A.
McIntire, Larry V.
Master of Science
There is a growing amount of evidence a significant link exists between the body's immune system and blood coagulation pathways. Specifically, the monocyte, a peripheral blood leukocyte, has been found to be the source of leukocyte tissue factor activity (TFA). This TFA activates the extrinsic blood clotting pathway. It is becoming apparent that there are two pathways for monocyte TFA production a lymphocyte dependent pathway and a lymphocyte independent pathway. Problems of blood clotting and thrombus formation in clinical situations include the use of extra-corporeal circulation and artificial heart valves. In addition disease states such as atherosclerosis and rheumatic heart disease are often associated with (or in some instances possibly caused by) coagulation abnormalities. These disease states also have in common non-physiologic levels of shear stress applied to the blood. The possibility exists that there is a significant link between the applied shear stress in the blood and the development of pathological coagulation. Since monocytes are known to be a source of TFA in response to various stimuli, this study was undertaken to measure monocyte TFA in response to shear stress. It was found that mechanical trauma could induce tissue factor production and that shear-induced TFA required the presence of lymphocytes. That the functional capability to produce TFA was there after shear stress in cells not producing TFA was demonstrated by subsequent treatment with endotoxin. Therefore, in clinical situations where mechanical trauma to leukocytes is a problem, the possibility of leukocyte TFA needs to be considered.