Intracellular trafficking of the α<sub>IIb</sub>β<sub>3</sub> receptor antagonist, abciximab, in normal and Glanzmann's disease megakaryocytes

Massé, Jean‐Marc; Perlemuter, Katy; Debili, Najet; Letestu, Rémi; Castaigne, A; Cramer, Elisabeth M.

doi:10.1046/j.1365-2141.1999.01768.x

Cited by 6 publications

(2 citation statements)

References 38 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abciximab does not normally significantly shorten platelet survival. Although it does bind to megakaryocytes (12,13), it does not appear to affect megakaryopoiesis.…”

Section: Abciximabmentioning

confidence: 98%

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

2001

View full text Add to dashboard Cite

SummaryThree platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been approved as adjunctive therapy to decrease the ischemic complications of percutaneous coronary interventions (PCI) and/or unstable angina. They include the chimeric murine/human monoclonal antibody 7E3 Fab fragment (abciximab), a cyclic heptapeptide based on the KGD amino acid sequence (eptifibatide), and a nonpeptide mimetic of the RGD sequence (tirofiban). The agents are very effective in providing both short-term and long-term benefit after PCI, and one agent has also demonstrated a progressive long-term mortality benefit. The long-term mortality benefit is highly cost-effective when compared to other medical interventions. The benefits in treating unstable angina without PCI are less dramatic and robust, with some agents providing no benefit. Severe thrombocytopenia is an infrequent, but potentially serious, complication of therapy with all of the agents. The risk of major bleeding is increased only minimally or not at all by the drugs. Currently, a number of new indications for GPIIb/IIIa antagonists are under study, including acute myocardial infarction (± thrombolytic therapy, ± PCI) and stroke. In addition to their impact on improving outcome, the results of clinical trials with these agents provide crucial insights into the contribution of GPIIb/IIIa-mediated platelet function in the pathophysiology of thrombotic vascular disease.

show abstract

“…Abciximab does not normally significantly shorten platelet survival. Although it does bind to megakaryocytes (12,13), it does not appear to affect megakaryopoiesis.…”

Section: Abciximabmentioning

confidence: 98%

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

2001

View full text Add to dashboard Cite

show abstract

“…Massé et al . demonstrated that abciximab, the blocking chimeric antibody fragment that targets α IIb β 3 receptor, may bind to MK plasma membrane and be secondarily internalized; thus, we tested whether a patient's autoantibody would follow a similar process. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

First description of an IgM monoclonal antibody causing αIIbβ3 integrin activation and acquired Glanzmann thrombasthenia associated with macrothrombocytopenia

Pillois

Guy

Choquet

et al. 2019

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Acquired Glanzmann thrombasthenia (GT) is generally caused by anti‐αIIbβ3 autoantibodies. We report the case of a man with an acquired GT phenotype associated with macrothrombocytopenia. Perturbed platelet function were associated with an activating anti‐αIIbβ3 IgM autoantibody. This novel clinical entity raises interesting questions about the αIIbβ3 integrin signaling. Summary BackgroundAcquired Glanzmann thrombasthenia (GT) is a bleeding disorder generally caused by anti‐αIIbβ3 autoantibodies. ObjectivesWe aimed to characterize the molecular mechanism leading to a progressive GT‐like phenotype in a patient with chronic immune thrombocytopenia. Patient, Methods, and ResultsThe patient suffered from repeated episodes of gastrointestinal bleeding; further studies indicated a moderate platelet aggregation defect. A few months later, platelet function showed abolished aggregation using all agonists, but normal agglutination with ristocetin. No platelet‐bound antibodies were detected, but the presence of large amounts of an IgM type antibody detected together with αIIbβ3 in the patient permeabilized platelets suggested that this IgM was an autoantibody causing the internalization of the complex. This was confirmed by the fact that the patient IgM bound to normal platelets but not to platelets from GT type I patients. Moreover, patient′s plasma activated αIIbβ3 on controls’ platelets as evidenced by increased PAC‐1 binding. We also demonstrated that the patient plasma triggered αIIbβ3 outside‐in signaling, as β3 Tyr773 and FAK were phosphorylated, and increased the rate of actin polymerization in resting platelets reflecting an impairment of cytoskeletal reorganization. Because different signs of dysmegakaryopoiesis were also observed in our patient, we evaluated the ability of its serum to impair proplatelets formation and showed that it significantly decreased the number of proplatelet‐bearing megakaryocytes in controls’ bone marrow stem cells culture compared with normal serum. ConclusionsWe present the case of a patient with a progressive and severely perturbed platelet function associated with the presence of an IgM activating autoantibody directed against αIIbβ3.

show abstract

Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS)

Giordano

Romano

Corcione

et al. 2018

J. of Cardiovasc. Trans. Res.

View full text Add to dashboard Cite

An unexpectedly high incidence of thrombosis in patients that received the polylactic acid bioresorbable vascular scaffold (BVS) suggests a delayed/incomplete endothelial repair with this stent. The anti-platelet agent tirofiban stimulates endothelial cell migration and proliferation, mediated by VEGF production. We investigated the tirofiban effect on the migration and adhesion of endothelial cells to BVS, in vitro. We performed human umbilical endothelial cell (HUVEC) cultures in the presence of BVS. Tirofiban, similarly to VEGF, increased the ability of HUVEC to grow on the vascular scaffold, compared to unstimulated or abciximab-treated cells. Tirofiban increased HUVEC expression of β1 and β3 integrins along with collagen and fibronectin. A role for β1 integrin in the "pro-adhesive and -migratory" signals elicited by tirofiban was suggested by use of an anti-β1-blocking antibody that prevented poly-levo-lactic acid vascular scaffold colonization. Our study suggests that tirofiban may improve the outcomes of patients receiving BVS by accelerating stent endothelization.

show abstract

Intracellular trafficking of the α_IIbβ₃ receptor antagonist, abciximab, in normal and Glanzmann's disease megakaryocytes

Cited by 6 publications

References 38 publications

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

First description of an IgM monoclonal antibody causing αIIbβ3 integrin activation and acquired Glanzmann thrombasthenia associated with macrothrombocytopenia

Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS)

Contact Info

Product

Resources

About

Intracellular trafficking of the αIIbβ3 receptor antagonist, abciximab, in normal and Glanzmann's disease megakaryocytes

Cited by 6 publications

References 38 publications

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

First description of an IgM monoclonal antibody causing αIIbβ3 integrin activation and acquired Glanzmann thrombasthenia associated with macrothrombocytopenia

Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS)

Contact Info

Product

Resources

About

Intracellular trafficking of the α_IIbβ₃ receptor antagonist, abciximab, in normal and Glanzmann's disease megakaryocytes