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Fibronectin: Extra Domain Brings Extra Risk?: Comment On Prakash Et Al, Page 3164
Fibronectin: Extra Domain Brings Extra Risk?: Comment On Prakash Et Al, Page 3164
Fibronectin: Extra Domain Brings Extra Risk?: Comment On Prakash Et Al, Page 3164
platelets.1 Using the FeCl3-induced carotid thrombosis, inflammation, and innate 4. Ni H, Yuen PS, Papalia JM, et al. Plasma fibronectin
promotes thrombus growth and stability in injured
injury intravital microscopy model, they immunity, in which both fibrin and NETs arterioles. Proc Natl Acad Sci USA. 2003;100(5):
found that Fn-EDA1/1 mice exhibited play a vital role (see figure). 2415-2419.
significantly enhanced thrombosis compared Platelets contain both pFn (;80% 5. Reheman A, Yang H, Zhu G, et al. Plasma fibronectin
with Fn-EDA2/2 mice. However, this of platelet Fn’s) and cFn. pFn is internalized depletion enhances platelet aggregation and thrombus
formation in mice lacking fibrinogen and von Willebrand
prothrombotic phenotype was abolished in through platelet surface aIIbb3 integrin,10 factor. Blood. 2009;113(8):1809-1817.
the absence of Toll-like receptor 4 (TLR4). whereas cFn is synthesized in megakaryocytes 6. Wang Y, Reheman A, Spring CM, et al. Plasma
They further demonstrated that Fn-EDA1 and packaged in platelets. Although present fibronectin supports hemostasis and regulates thrombosis.
targets TLR4 in hematopoietic lineage cells at relatively small amounts, these Fn’s can J Clin Invest. 2014;124(10):4281-4293.
following bone marrow transplants with be released from a-granules upon platelet 7. Chauhan AK, Kisucka J, Cozzi MR, et al.
Prothrombotic effects of fibronectin isoforms containing
or without TLR4 expression (EDA1/1/ activation and boost the Fn concentration at the the EDA domain. Arterioscler Thromb Vasc Biol. 2008;
TLR41/1 or EDA1/1/TLR42/2) into site of thrombosis (see figure). With an increase 28(2):296-301.
Fn-EDA1/1 mice. Finally, after depletion of in Fn-EDA1 in blood plasma, the platelet 8. Maurer E, Receveur N, Bourdon C, et al. Integrin a5b1
endogenous platelets in Fn-EDA1/1 mice, Fn-EDA1 likely also increases via aIIbb3 and glycoprotein VI play important roles in mediating
activation and aggregation of platelets adhering to fibrillar
mice transfused with EDA1/1/TLR41/1 integrin internalization. Could the platelet fibronectin. In: Proceedings from the XXIV Congress of
but not EDA1/1/TLR42/2 platelets showed endogenous Fn-EDA1 also contribute to International Society on Thrombosis and Haemostasis
(ISTH); June 29-July 4, 2013; Amsterdam, The
enhanced thrombosis, thus localizing the thrombosis? Another interesting fact is that Netherlands. Abstract OC 87.3.
downstream of Fn-EDA1 prothrombotic platelet aggregation and thrombus formation
9. Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4
function to platelet TLR4. In addition, persist in the absence of both fibrinogen and activates neutrophil extracellular traps to ensnare bacteria
activation of a downstream nuclear factor kB von Willebrand factor (VWF), 2 factors in septic blood. Nat Med. 2007;13(4):463-469.
(NF-kB) signaling pathway within the platelet previously considered essential for thrombosis. 10. Ni H, Papalia JM, Degen JL, Wagner DD. Control of
thrombus embolization and fibronectin internalization by
was found following TLR4 activation by The platelet content of Fn in fibrinogen- and
integrin aIIbb3 engagement of the fibrinogen g chain.
Fn-EDA1. This informative study reveals VWF-deficient animals is threefold to fivefold Blood. 2003;102(10):3609-3614.
a novel Fn-EDA1 and platelet TLR4 higher. Although pFn has been subsequently
interaction that contributes to thrombosis, ruled out as the factor to mediate fibrinogen- © 2015 by The American Society of Hematology