Association of thrombospondin-1 with the actin cytoskeleton of human thrombin-activated platelets through an αIIbβ3- or CD36-independent mechanism

Abstract

Thrombospondin-1 (TSP-1) is an adhesive glycoprotein which, when secreted from α-granules of activated platelets, can bind to the cell surface and participate in platelet aggregate formation. In this study, we show that thrombin activation leads to the rapid and specific association of a large amount of secreted α-granular TSP-1 with the actin cytoskeleton. This cytoskeletal association of TSP-1 was correlated with platelet secretion, but not aggregation, and was inhibited by cytochalasin D, an inhibitor of actin polymerization. Association of TSP-1 with the actin cytoskeleton was mediated by membrane receptors, as shown by using MAII, a TSP-1-specific monoclonal antibody that inhibited both TSP-1 surface binding to activated platelets and cytoskeletal association. TSP-1 and its potential membrane receptors, e.g. αIIbβ3 integrin, CD36 and CD47, concomitantly associated with the actin cytoskeleton. However, studies on platelets from a patient with type I Glanzmann's thrombasthenia lacking αIIbβ3 and another with barely detectable CD36 showed normal TSP-1 surface expression and association with the actin cytoskeleton.

Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function

“…Leukocyte surface antigen (CD47) and CD44 on the exosome surface both bind glycoproteins identified on the MDSC surface , and CD29 and CD172a on the MDSC surface bind to TSP-1 , and fibrinogen, respectively, identified on the exosome surface. Most of the cell surface molecules listed in Table are also receptors or ligands expressed by other cells in the tumor microenvironment. − Our survey appears to support adhesion between exosomes and cells, though not yet selective recognition.…”

Signaling role of CD36 in platelet activation and thrombus formation on immobilized thrombospondin or oxidized low‐density lipoprotein

“…Another report proposes that TSP1 binding cancels the inhibiting effects of nitric oxide on platelets [27]. Furthermore, also integrin‐dependent ways of TSP1 action on platelets have been reported [28]. Altogether, there appears to be a similarity in the action mechanisms of oxLDL and TSP1 on platelets, which raises the question whether this involves common signaling events via CD36.…”

The use of CD47-modified biomaterials to mitigate the immune response

“…TSP-1, a known CD47 ligand, is primarily secreted from alpha granules of activated platelets. [64][65][66] TSP-1 has been shown, via interactions with CD47, to exacerbate ischemia reperfusion injury by inhibiting signaling events mediated by NO. [64][65][66] Thus, it is tempting to hypothesize that the SIRPa expression on platelets represents a feedback mechanism to limit the release of TSP-1 from platelet granules.…”

“…64–66 TSP-1 has been shown, via interactions with CD47, to exacerbate ischemia reperfusion injury by inhibiting signaling events mediated by NO. 64–66 Thus, it is tempting to hypothesize that the SIRPα expression on platelets represents a feedback mechanism to limit the release of TSP-1 from platelet granules. Indeed, myosin 2a and actin have all been implicated in playing a role in a granule release.…”