Interaction of fibrinogen with its platelet receptor: kinetics and effect of pH and temperature

Marguerie, G; Plow, Edward F.

doi:10.1021/bi00508a005

Cited by 67 publications

(29 citation statements)

References 23 publications

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“…The blood from 8 donors was tested at six temperatures (15,20,24,28,32, and 37°C). Due to the time required for CPF analysis, only three temperatures could be tested simultaneously, therefore three 60-cc syringes of blood were drawn from the same donor for a given experiment, and each syringe was exposed to a dierent temperature (all three simultaneously), as summarized in Table I.…”

Section: Experimental Design To Examine the Effect Of Temperaturementioning

confidence: 99%

Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation

Hall¹,

Goodman²,

Alston³

et al. 2001

American J Hematol

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Cold-induced platelet aggregation (CIPA) in PRP has previously been documented in connection with platelet preservation (4±15°C). This report describes hypothermia-induced platelet aggregation (HIPA) in whole blood and at temperatures used in open-heart surgery (24±32°C). HIPA (speci®cally, the formation of occlusive aggregates) was studied in human whole blood. Fresh heparinized (1.5 U/ml) human blood was cooled and maintained at target temperatures (15, 20, 24, 28, 32, or 37°C) as it¯owed (1 ml/min) through 75-cm long 1/32" internal diameter polymer conduit. The formation of aggregates in the tubing was veri®ed using optical video microscopy and was quanti®ed by a lightscattering method and a constant-pressure ®ltration method. Donors were tested at least twice at each target temperature and were classi®ed into three separate response regimes (Low, Medium, and High) on the basis of the number of aggregates and the duration of their appearance. The screening of 121 donors (average age 22.3 4.3 years) for HIPA at 24°C (the temperature of maximum response) indicated 14% High Responders, 18% Medium Responders, and 68% Low Responders. HIPA was inhibited by EDTA, citrate, PGE 1 , and Tiro®ban, but not by aspirin, and it was enhanced by elevated heparin levels. HIPA was consistently noted in the blood of a subpopulation of donors, and the associated platelet aggregates in the blood of High Responders were rigid and occlusive. It is postulated that such aggregates may contribute to cognitive dysfunction noted in patients undergoing hypothermic open-heart surgery, and that postulus is being investigated. Am.

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Section: Experimental Design To Examine the Effect Of Temperaturementioning

confidence: 99%

Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation

Hall¹,

Goodman²,

Alston³

et al. 2001

American J Hematol

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“…7.2 [21]. The comparison of the binding of '"I-Fg and ' "1-Fg-SANAH to the platelets was performed using assay systems as previously described [20]. Typically, platelets at 108 cellsiml, suspended in Tyrode's-2 albumin buffer, pH 7.2, were incubated in the presence of 0.1 pM '2sI-Pg or '"I-Fg-SANAH and stimulated with I0 pM ADP in the presence of 0.5 m M calcium.…”

Section: Binding Qf L2'1-fg Atid '"I-and-sanah Fo Plateletsmentioning

confidence: 99%

The platelet‐fibrinogen interaction

Marguerie

Thomas-Maison

Ginsberg

et al. 1984

European Journal of Biochemistry

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Fibrinogen participates in platelet aggregation via specific inducible receptors on the cell surface. We have used a photoactivable bifunctional reagent, N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate, SANAH, to derivatize '2s1-labeled-fibrinogen (I2'1-Fg) and crosslink it to ADP-stimulated platelets. Binding experiments established that 1251-Fg and Iz5I-Fg-SANAH interacted with platelets with the same kinetics and affinity as unlabeled fibrinogen. After photoactivation of the platelet-bound '251-Fg-SANAH, polyacrylamide gel electrophoresis under reducing conditions revealed formation of a high molecular weight covalent complex with coordinate loss of the A a chain. I2'I-Fg-SANAH missing the extreme carboxy-terminal region of the Aa chain failed to crosslink to the platelets under similar conditions. Crosslinked "'1-Fg-SANAH was extracted from the cells in 1 % Triton X-100, and immunoprecipitation with antibodies specific for platelet membrane glycoproteins was used to identify components of the complex. With antibodies to the glycoprotein IIb/III complex (anti-GP IIb/III), 40 9 % of the extracted "'I-Fg-SANAH was irnmunoprecipitated. Omission of photoactivation, platelets, or ADP from the reaction or use of unmodified lZ5I-Fg resulted in less than 5 % immunoprecipitation by the anti-GP IIb/III. As controls for specificity, anti-(glycoprotein Ib) or anti-IgG immunoprecipitated less than 5 % of the extracted I2%Fg-SANAH. Under similar conditions, 45 "/, of the GP lTb/III from surface-labeled platelets was recovered in the antiGPITb/IIT immunoprecipitate. These results indicate that the Aa chain of fibrinogen comes in close proximity to GP IIb/III when the molecule is bound to its platelet receptor.Stimulated platelets interact with one another to form aggregates, a process essential to primary hemostasis. Fibrinogen may participate in this reaction by interacting with specific inducible rceptors on the platelet surface [l, 21, and receptor occupancy is closely related to the aggregation response of the platelets [3, 41. Recent studies have implicated two of the surface membrane glycoproteins, designated GP 1Ib and GF' 111, in platelet aggregation and fibrinogen receptor function. These two glycoproteins have apparent molecular weights of 136000 (GP IIb) and 95000 (GPIII) on polyacrylamide gel electrophoresis under n onreducing conditions [5] and form a noncovalent complex, GP Ilb,/III, in the presence of calcium [6-81. Thrombasthenic platelets, which generally lack both GP IIb and GP 111 [9, 201, do not aggregate in response to most platelet stimuli [Ill and fail to express the majority of fibrinogen binding sites [l].Other observations which also support a role for GP lIb/III in fibrinogen receptor function include: (a) an 1gG alloantibody directed against the G P IIb/III inhibits fibrinogen binding to platelets [12]; (b) partially purified GP IIb/III associates with fibrinogen in the presence of calcium in a solid __-_Ahbrevhtiunst SANAH, Succinimidyl-6-(4'-a~ido-2'-nitrophenylamino) hexanoate; lZ5I-...

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“…These contacts can lead to cellular adhesion, migration, and activation (4 -6). In a number of cell types, such as platelets and leukocytes, the activities of integrins are tightly regulated such that host cell activation is required before cell binding can proceed (7)(8)(9). This prerequisite ensures that integrin function is operative only at the appropriate anatomical or pathological sites.…”

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confidence: 99%

Integrin Activation by Dithiothreitol or Mn2+ Induces a Ligand-occupied Conformation and Exposure of a Novel NH2-terminal Regulatory Site on the β1Integrin Chain

Simonsen

et al. 1998

Journal of Biological Chemistry

112

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Integrins can be expressed in at least three functional states (i.e. latent, active, and ligand-occupied). However, the molecular bases for the transitions between these states are unknown. In the present study, changes in the accessibility of several ␤ 1 epitopes (e.g. N29, B44, and B3B11) were used to probe activation-related conformational changes. Dithiothreitol or Mn 2؉ activation of integrin-mediated adhesion in the human B cell line, IM9, resulted in a marked increase in the exposure of the B44 epitope, while N29 expression levels were most sensitive to dithiothreitol treatment. These results contrasted with the epitope expression patterns of spontaneously adherent K562 cells, where N29 was almost fully accessible and B44 was low. Addition of a soluble ligand resulted in a marked increase in B44 levels, suggesting that this antibody detected a ligand-induced binding site. The N29 epitope was mapped to a cysteine-rich region near the NH 2 terminus of the integrin chain, thus defining a novel regulatory site.These studies indicate that the activation of integrin function by different stimuli may involve related but nonidentical conformations. Both Mn 2؉ and dithiothreitol appear to induce localized conformational changes that mimic a ligand-occupied receptor. This differs from the "physiologically" activated integrins on K562 cells that display a marked increase in overall epitope accessibility without exposure of the ligand-induced binding site epitopes. The increased exposure of the N29 site on K562 cells may indicate a role for this region in the regulation of integrin function.

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Interaction of fibrinogen with its platelet receptor: kinetics and effect of pH and temperature

Cited by 67 publications

References 23 publications

Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation

Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation

The platelet‐fibrinogen interaction

Integrin Activation by Dithiothreitol or Mn2+ Induces a Ligand-occupied Conformation and Exposure of a Novel NH2-terminal Regulatory Site on the β1Integrin Chain

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