Soluble TLT-1 modulates platelet-endothelial cell interactions and actin polymerization.
Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) is a membrane protein receptor found in alpha-granules of platelets and megakaryocytes. Upon platelet activation TLT-1 is rapidly brought to the surface of platelets. Recently, we demonstrated that activated platelets release a soluble form of TLT-1 (sTLT-1) that is found in serum but not in the plasma of healthy individuals and can enhance platelet aggregation in vitro. Furthermore, evaluation of patients diagnosed with inflammatory diseases, such as sepsis, show that these patients have significantly elevated levels of sTLT-1 in their blood. Accordingly, mice deficient in TLT-1 are predisposed to bleeding in response to an inflammatory challenge; however, the mechanism of TLT-1 function remains unknown. In this investigation, we demonstrate an increase in the amount of platelets that adhere to endothelial cell monolayers in the presence of recombinant sTLT-1 (rsTLT-1). Additionally, we present evidence that rsTLT-1 increases platelet adherence to glass slides by stimulating actin polymerization in platelets, as determined by increased staining of rodamine phalloidin. These results suggest that during inflammation, sTLT-1 may mediate hemostasis by enhancing actin polymerization, resulting in increased platelet aggregation and adherence to the endothelium.
Morales
Jessica
J
Laboratory of Anatomy and Cell Biology, Universidad Central del Caribe, Bayamón, Puerto Rico.
Villa
Karina
K
Gattis
Jim
J
Castro
William
W
Colon
Katiria
K
Lubkowski
Jacek
J
Sanabria
Priscilla
P
Hunter
Robert
R
Washington
A Valance
AV
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D002417:Cattle; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D011971:Receptors, Immunologic; C473366:TREML1 protein, human