Platelet-mediated collagen and fibrin retraction: Effect of prostaglandins, cyclic AMP, calcium antagonists and N-ethylmaleimide

Jeleńska, M.M.; Kopeć, M

doi:10.1016/0049-3848(83)90184-6

Cited by 10 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…54,55 Chelating divalent cations with EDTA essentially eliminates the interaction of fibrinogen with the RGD binding pocket, but the effects of EDTA on clot retraction are complex. A requirement for Ca 21 in clot retraction was reported by Budtz-Olsen in 1951, 56 and Jelenska and Kopeć 57 reported complete inhibition of clot retraction by EDTA in a washed-platelet system in which thrombin was used to initiate clot formation. Carr et al 58 force development.…”

Section: Discussionmentioning

confidence: 77%

Dominant role of αIIbβ3 in platelet interactions with cross-linked fibrin fragment D-dimer

et al. 2020

View full text Add to dashboard Cite

Although much is known about the interaction of fibrinogen with αIIbβ3, much less is known about the interaction of platelets with cross-linked fibrin. Fibrinogen residue Lys406 plays a vital role in the interaction of fibrinogen with αIIbβ3, but because it participates in fibrin cross-linking, it is not available for interacting with αIIbβ3. We studied the adhesion of platelets and HEK cells expressing normal and constitutively active αIIbβ3 to both immobilized fibrinogen and D-dimer, a proteolytic fragment of cross-linked fibrin, as well as platelet-mediated clot retraction. Nonactivated platelets and HEK cells expressing normal αIIbβ3 adhered to fibrinogen but not D-dimer, whereas activated platelets as well as HEK cells expressing activated αIIbβ3 both bound to D-dimer. Small-molecule antagonists of the αIIbβ3 RGD (Arg-Gly-Asp) binding pocket inhibited adhesion to D-dimer, and an Asp119Ala mutation that disrupts the β3 metal ion–dependent adhesion site inhibited αIIbβ3-mediated adhesion to D-dimer. D-dimer and a polyclonal antibody against D-dimer inhibited clot retraction. The monoclonal antibody (mAb) 10E5, directed at αIIb and a potent inhibitor of platelet interactions with fibrinogen, did not inhibit the interaction of activated platelets with D-dimer or clot retraction, whereas the mAb 7E3, directed at β3, inhibited both phenomena. We conclude that activated, but not nonactivated, αIIbβ3 mediates interactions between platelets and D-dimer, and by extrapolation, to cross-linked fibrin. Although the interaction of αIIbβ3 with D-dimer differs from that with fibrinogen, it probably involves contributions from regions on β3 that are close to, or that are affected by, changes in the RGD binding pocket.

show abstract

Section: Discussionmentioning

confidence: 77%

Dominant role of αIIbβ3 in platelet interactions with cross-linked fibrin fragment D-dimer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A number of other laboratories have examined'second messengers that regulate matrix contraction by fibroblasts. Several studies have confirmed the role of cAMP and CAMP-dependent kinases in regulating matrix contraction (Jelenska and Kopec, 1983;Ehrlich and Griswold, 1984;Van Bockxmeer et al, 1984). In these cases, agents that elevated cAMP levels inhibited fibroblast contraction.…”

Section: Discussionmentioning

confidence: 91%

Fibroblast contraction of collagen gels requires activation of protein kinase C

Guidry

1993

Journal Cellular Physiology

View full text Add to dashboard Cite

Fibroblasts stimulated to contract collagen gels with serum were completely inhibited by staurosporine, a broad spectrum kinase inhibitor. Further analysis demonstrated that staurosporine is potent (IC50 17 nM), rapid in onset, and completely reversible. Complete inhibition of gel contraction was also observed with calphostin C (IC50 48 nM), an inhibitor specific for protein kinase C (PKC). Similar effects were not observed with KT5926 or KT5720, inhibitors for myosin light chain kinase and cAMP-dependent kinases, respectively. These data suggested that serum-stimulated fibroblast contraction is dependent upon activation of PKC. This was also observed with fibroblast contraction stimulated with endothelin-1, platelet-derived growth factor, and transforming growth factor beta. PKC activated directly with low concentrations of phorbol ester was observed to stimulate fibroblast contraction of collagen gels, in some cases within 30 minutes of exposure.

show abstract

“…There are at least11proteinswith free thiols on the plateletsurface (2), and more mayb eg enerated upon activation (3). Blockingt he free thiolsw ith N-ethylmaleimide (NEM)i nhibitsp lateleta ggre-gation and clot retraction (3)(4)(5), whereas disulfide-bond reducing agents DTT(dithiothreitol)and β-mercaptoethanol promote aggregation (6,7). Second, redoxa gents such as nitric oxide, S-nitrosothiols (8,9), low-molecular-weightthiols,and reduced glutathione (GSH) have beendemonstrated to affect platelet activation and aggregation (10).…”

Section: Introductionmentioning

confidence: 99%

Glutathione regulates integrin αIIbβ3-mediated cell adhesion under flow conditions

Ball¹,

Vijayan²,

Nguyen³

et al. 2008

Thromb Haemost

View full text Add to dashboard Cite

The platelet integrin alpha(IIb)beta(3) mediates the final step of platelet aggregation that requires pre-activation through an inside-out signal initiated by agonists. Experiments conducted under static conditions using platelet-rich plasma show that platelet activation and adhesion activity of alpha(IIb)beta(3) are regulated by glutathione (GSH-GSSG) redox potential. However, it remains unclear as to whether GSH-GSSG exerts its regulatory role in platelets by direct targeting of alpha(IIb)beta(3) or intracellular signals that activate the integrin. A role of fluid shear stress is also not known. We examined the effects of GSH-GSSG on the adhesion of CHO cells expressing two HPA variants of human alpha(IIb)beta(3) to the immobilized fibrinogen and von Willebrand factor (VWF) under flow conditions. GSH-GSSG dose-dependently reduced the number of adherent cells to fibrinogen and VWF under 2.5 dyn/cm(2) of shear stress, a physical force calculated to be 110 dyne on platelets. GSH treatment also abolished the hyper-adhesion activity of cells expressing the Pro33 variant of alpha(IIb)beta(3). The inhibition was also observed with washed platelets. The data differ from the early observation that GSH enhanced platelet aggregation induced by sub-threshold concentrations of platelet agonists. The results suggest that GSH may have distinct effects on agonist-induced alpha(IIb)beta(3) activation and on the alpha(IIb)beta(3)-fibrinogen or alpha(IIb)beta(3)-VWF bonds when exposed to fluid shear stress. They further suggest that the HPA phenotype may be redox-regulated.

show abstract

Platelet-mediated collagen and fibrin retraction: Effect of prostaglandins, cyclic AMP, calcium antagonists and N-ethylmaleimide

Cited by 10 publications

References 26 publications

Dominant role of αIIbβ3 in platelet interactions with cross-linked fibrin fragment D-dimer

Dominant role of αIIbβ3 in platelet interactions with cross-linked fibrin fragment D-dimer

Fibroblast contraction of collagen gels requires activation of protein kinase C

Glutathione regulates integrin αIIbβ3-mediated cell adhesion under flow conditions

Contact Info

Product

Resources

About