Exposure of platelet fibrinogen receptors by ADP and epinephrine.

Bennett, Joel S.; Vilaire, Gaston

doi:10.1172/jci109597

Cited by 863 publications

(413 citation statements)

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“…This has been demonstrated in ligand binding studies with odlbB3 (21)(22)(23)(24), c~MB2 (25) and oe5/31 (26,27). The increase in affinity of ot5~1 for soluble fibronectin was induced by the anti-131 monodonal antibody 8A2 (28), which is one of a group of antibodies that increase/31-mediated cellular adhesion to immobilized ligands (29)(30)(31).…”

mentioning

confidence: 59%

Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.

Faull

Kovach

Harlan

et al. 1994

The Journal of Experimental Medicine

138

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SummaryWe show that the adhesion of T lymphoid cells to immobilized fibronectin can be increased by two distinct mechanisms. The first is by increasing the affinity of the fibronectin receptor/ligand interaction using the antiq~l integrin monodonal antibody 8A2. The second is by treating the ceUs with phorbol 12-myristate 13-acetate (PMA), which alters events that occur after receptor occupancy (e.g., cell spreading) without affecting receptor affinity. The effects of these two mechanisms on adhesion in the presence of physiological concentrations of soluble fibronectin suggest that they have different biological consequences. Under these conditions, the net effect of increasing the affinity of the fibronectin receptors is to decrease cell adhesion, whereas the increase in adhesion induced by PMA is unaffected. This suggests that the high affinity receptors are not primarily available for cell adhesion under these circumstances, and that they have an alternative function. We further show that high affinity binding of soluble fibronectin can be induced by either differentiation of the monocytic cell line THP-1 or by cross-linking the T cell receptor complexes on the T lymphoid cell line HUT-78. The differentiated monocytic cells express two populations of fibronectin receptors: a minority in a high affinity state, and the majority in a low affinity state. Thus they will both continue to adhere in the presence of physiological concentrations of soluble fibronectin and bind significant amounts of soluble fibronectin at the cell surface.

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mentioning

confidence: 59%

Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.

Faull

Kovach

Harlan

et al. 1994

The Journal of Experimental Medicine

138

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“…The prototypical example of this form of regulation is the platelet integrin ␣ IIb ␤ 3 since agonist-generated "inside-out" signals are required to enable ␣ IIb ␤ 3 to bind soluble ligands such as fibrinogen (1). Because the binding of soluble fibrinogen to ␣ IIb ␤ 3 is a prerequisite for platelet aggregation (2), regulating the affinity of ␣ IIb ␤ 3 for fibrinogen in this way assures that only stimulated platelets aggregate. It is likely that intracellular molecules regulate the function of ␣ IIb ␤ 3 by interacting with its cytoplasmic domains (3), but the identity of these molecules and how they interact with ␣ IIb ␤ 3 are not known.…”

mentioning

confidence: 99%

The Platelet Cytoskeleton Regulates the Affinity of the Integrin αIIbβ3 for Fibrinogen

Bennett

Zigmond

Vilaire

et al. 1999

Journal of Biological Chemistry

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Agonist-generated inside-out signals enable the platelet integrin ␣ IIb ␤ 3 to bind soluble ligands such as fibrinogen. We found that inhibiting actin polymerization in unstimulated platelets with cytochalasin D or latrunculin A mimics the effects of platelet agonists by inducing fibrinogen binding to ␣ IIb ␤ 3 . By contrast, stabilizing actin filaments with jasplakinolide prevented cytochalasin D-, latrunculin A-, and ADP-induced fibrinogen binding. Cytochalasin D-and latrunculin A-induced fibrinogen was inhibited by ADP scavengers, suggesting that subthreshold concentrations of ADP provided the stimulus for the actin filament turnover required to see cytochalasin D and latrunculin A effects. Gelsolin, which severs actin filaments, is activated by calcium, whereas the actin disassembly factor cofilin is inhibited by serine phosphorylation. Consistent with a role for these factors in regulating ␣ IIb ␤ 3 function, cytochalasin D-and latrunculin A-induced fibrinogen binding was inhibited by the intracellular calcium chelators 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester and EGTA acetoxymethyl ester and the Ser/Thr phosphatase inhibitors okadaic acid and calyculin A. Our results suggest that the actin cytoskeleton in unstimulated platelets constrains ␣ IIb ␤ 3 in a low affinity state. We propose that agonist-stimulated increases in platelet cytosolic calcium initiate actin filament turnover. Increased actin filament turnover then relieves cytoskeletal constraints on ␣ IIb ␤ 3 , allowing it to assume the high affinity conformation required for soluble ligand binding.The function of integrins in circulating blood cells is regulated by limiting their access to ligands. The prototypical example of this form of regulation is the platelet integrin ␣ IIb ␤ 3 since agonist-generated "inside-out" signals are required to enable ␣ IIb ␤ 3 to bind soluble ligands such as fibrinogen (1). Because the binding of soluble fibrinogen to ␣ IIb ␤ 3 is a prerequisite for platelet aggregation (2), regulating the affinity of ␣ IIb ␤ 3 for fibrinogen in this way assures that only stimulated platelets aggregate. It is likely that intracellular molecules regulate the function of ␣ IIb ␤ 3 by interacting with its cytoplasmic domains (3), but the identity of these molecules and how they interact with ␣ IIb ␤ 3 are not known.The actin cytoskeleton appears to play a role in regulating ␣ IIb ␤ 3 function. Thus, micromolar concentrations of cytochalasins, fungal metabolites that impair actin polymerization by binding to the barbed end of actin filaments (4), inhibit agonistinduced fibrinogen binding to ␣ IIb ␤ 3 on platelets (5-7), whereas nanomolar concentrations induce fibrinogen binding to recombinant ␣ IIb ␤ 3 expressed on the surface of B lymphocytes (8). In the work described in this paper, we used cytochalasin D (Cyto-D), 1 latrunculin A (Lat-A; another inhibitor of actin polymerization (9)), and jasplakinolide (a compound that stabilizes actin filaments (10)) to examine the role of actin filament turnover in...

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“…a,,,,/& on the surface of resting platelets does not bind soluble macromolecular ligands such as fibrinogen under conditions of normal circulation [3]. However, when platelets are exposed to appropriate agonists, the fibrinogen-binding affinity of is markedly increased [3, 41 probably due to a conformational change in the integrin 15, 61.…”

mentioning

confidence: 99%

“…The proposed sites on the fibrinogen molecule that interact with the a,,,$, complex are a dodecapeptide HHLGGAK-QAGDV (His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val, H-12-V) corresponding to the C-terminus of the fibrinogen y chain 11 [1][2][3][4][5][6][7][8][9][10][11][12][13], and a tetrapeptides RGDS (Arg-Gly-Asp-Ser) or RGDF (Arg-Gly-Asp-Phe) corresponding to the Arx chain sequences 572-575 and 95-98, respectively 114-181. The synthetic peptide analogues o f these peptides inhibit platelet aggregation and fibrinogen binding to activated platelets, and are mutually inhibitory in binding studies .…”

mentioning

confidence: 99%

Microenvironmental Changes in Platelet Membranes Induced by the Interaction of Fibrinogen‐Derived Peptide Ligands with Platelet Integrins

Watała

Gwoździński

Pluskota

et al. 1996

European Journal of Biochemistry

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A few studies have confirmed the influence of peptides containing either the RGD or dodecapeptide H-I 2-V (HHLGGAKQAGDV) sequence on cell membrane structure and function. In order to consider previous findings and to explore microenvironmental changes associated with the interaction of these two fibrinogen-derived peptides with platelet membranes, we employed fluorescence quenching and electron paramagnetic resonance techniques to monitor the possible alterations in platelet membrane dynamics induced by RGDS and H-12-V. The interaction of RGDS with platelet membranes resulted in reduced values of the h+,/h,, parameter in both 5-doxylstearic acid and 16-doxylstearic acid spectra indicating a significant rigidification of the membrane lipid bilayer. Otherwise, the fibrinogen-derived peptide that contained the y chain C-terminal sequence H-12-V had a fluidizing effect on the platelet membrane lipid bilayer. The labelling of platelet membranes with 1 -anilino-8-naphthalenesulphonate (ANS) enabled us to estimate the energy transfer efficiency and the apparent interchromophore distance between membrane protein tryptophan and ANS embedded into the membrane lipid bilayer. As RGDS interacts with platelet membrane this distance decreases, resulting in the relevant increase of energy transfer efficiency. The opposite alterations were recorded upon interaction of platelet membranes with H-I 2-V. Furthermore, a small shift towards longer wavelengths, which accompanies the spectra of ANS in control platelet membranes, vanishes during the interaction with the peptide H-12-V. This observation can be accounted for by a decrease in the polarity of the ANS environment, and may suggest an enhanced contact of the membrane tryptophan with phospholipid fatty acids. Thus, the data indicate that after the action of H-I 2-V on platelet membrane receptors, the membrane tryptophan residues become exposed to the external environment and the quenchable fraction of membrane tryptophan becomes smaller. The increase (a) in the relative rotational correlation time (z,) of 4-(ethoxyfluorophosphinyloxy)-2,2,6,6-tetramethylpiperidine-I -oxyl (ethoxyfluorophosphinyloxy-TEMPO) and (b) in the hJh, ratio in the spectra of 4-maleimido-2,2,6,6-tctramethylpiperidine-l -oxyl (maleimido-TEMPO) indicate that under these conditions there is an effective immobilization of some domains located on the hydrated surface of membrane proteins and mobilization of those domains buried inside the membrane protein molecules. The interaction of RGDS with platelet membrane integrins resulted in contrary effects, as compared to H-12-V. In conclusion, our spectroscopic data indicate that these two fibrinogen-derived peptides induce opposite effects in the dynamics of platelet membrane components. hexapeptide Gly-Arg-Gly-Glu-Ser-Pro; H-12-V, dodecapeptidc His-HisLeu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-~~1; h , ,/h,,, the ratio of lowfield to mid-field line heights in 5/16-DOXYL-Ste spectra; 12, and /I,, low-field line heights corresponding to weakly and strongly immobilized male...

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Exposure of platelet fibrinogen receptors by ADP and epinephrine.

Abstract: A B S T R A C T The role of fibrinogen as a cofactor for platelet aggregation was examiined by measuring the binding of 1251-labeled hulnan fibrinogen to gelfiltered human platelets both before and after platelet stimulation by ADP and

Cited by 863 publications

References 32 publications

Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.

Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.

The Platelet Cytoskeleton Regulates the Affinity of the Integrin αIIbβ3 for Fibrinogen

Microenvironmental Changes in Platelet Membranes Induced by the Interaction of Fibrinogen‐Derived Peptide Ligands with Platelet Integrins

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