Submitted May 15, 2006
Accepted June 23, 2006
Anti-adhesive effect of fibrinogen: A safeguard for
thrombus stability
Valeryi K Lishko, Timothy Burke, and Tatiana Ugarova*
Cleveland Clinic Foundation, Cleveland, OH, USA
Joseph J. Jacobs Center for Thrombosis & Vascular Biology, Lerner Research Institute, Cleveland, OH
* Corresponding author; email: ugarovt{at}ccf.org.
The recruitment of phagocytic leukocytes to sites of
vessel wall injury plays an important role in thrombus
dissolution by proteases elaborated upon their adhesion.
However, leukocyte adhesion to the fibrin clot can be
detrimental at the early stages of wound healing when
hemostatic plug integrity is critical for preventing
blood loss. Adhesion of circulating leukocytes to the
insoluble fibrin(ogen) matrix is mediated by integrins
and occurs in the presence of high concentration of
plasma fibrinogen. In this study, the possibility that
soluble fibrinogen could protect fibrin from excessive
adhesion of leukocytes was examined. Fibrinogen was a
potent inhibitor of adhesion of U937 monocytoid cells
and neutrophils to fibrin gel and immobilized fibrin
(ogen). An investigation of the mechanism by which
soluble fibrinogen exerts its influence on leukocyte
adhesion indicated that it did not block integrins but
rather associated with the fibrin(ogen) substrate.
Consequently, leukocytes that engage fibrinogen
molecules loosely bound to the surface of fibrin(ogen)
matrix are not able to consolidate their grip on the
substrate; subsequently, cells detach. This conclusion
is based on the evidence obtained in adhesion studies
using various cells and performed under static and flow
conditions. These findings reveal a new role of
fibrinogen in integrin-mediated leukocyte adhesion and
suggest that this mechanism may protect the thrombus
from premature dissolution.
