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Intracellular trafficking of the α IIb β 3 receptor antagonist, abciximab, in normal and Glanzmann's disease megakaryocytes
Author(s) -
Massé JeanMarc,
Perlemuter Katy,
Debili Najet,
Letestu Rémi,
Castaigne Alain,
Cramer Elisabeth M.
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01768.x
Subject(s) - abciximab , platelet , platelet membrane glycoprotein , platelet glycoprotein gpiib iiia complex , receptor , antagonist , platelet activation , thrombasthenia , chemistry , medicine , pharmacology , endocrinology , platelet aggregation , myocardial infarction , conventional pci
The α IIb β 3 platelet receptor antagonist abciximab (c7E3Fab, ReoPro ® ) has proved to be effective in preventing arterial thrombosis. However, its binding capacity to the platelet precursors, megakaryocytes (MKs), which also express α IIb β 3 , is not known. The purpose of this study was to establish whether abciximab is able to react with α IIb β 3 located on human MKs, and to follow its subsequent intracellular trafficking. MKs were grown from CD34 + progenitors from normal subjects and from a patient with type I Glanzmann's thrombasthenia, and abciximab was added at day 10 of culture (4 μg/ml). Cells were fixed at day 12, cryosectioned, and immunolabelled for abciximab. Labelling was prominent on the MK plasma membrane; it also lined the demarcation membration system. Interestingly, α‐granule membranes were labelled showing that the antibody was internalized and further stored into MK secretory granules. Abciximab was also strongly detected on and in newly‐formed platelets. Glanzmann's disease MKs (which completely lacked α IIb β 3 ) were consistently negative, confirming that the antibody fragment was specifically interacting with α IIb β 3 . In conclusion, this study demonstrated that abciximab: (i) binds MK plasma membrane and demarcation membranes, (ii) trafficks into α‐granules, and (iii) is expressed on and in nascent platelets. These findings could be taken in account when monitoring anti‐α IIb β 3 receptor therapy.