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Platelet fibrinogen and vitronectin in Glanzmann thrombasthenia: evidence
consistent with specific roles for glycoprotein IIb/IIIA and alpha v beta 3
integrins in platelet protein trafficking [see comments]
BS Coller, U Seligsohn, SM West, LE Scudder and KJ Norton
Department of Medicine, State University of New York, Stony Brook 11794.
To assess the individual contributions of the platelet glycoprotein (GP)
IIb/IIIa receptor and the alpha v beta 3 vitronectin receptor to platelet
levels of fibrinogen and vitronectin, we analyzed the platelets from two
groups of Glanzmann thrombasthenic patients: Iraqi- Jews, whose platelets
lack both receptors, and Arab patients in Israel, whose platelets lack
GPIIb/IIIa, but have normal or increased numbers of alpha v beta 3
vitronectin receptors. The platelets from both thrombasthenic groups had
profound deficiencies of fibrinogen, but the defect in the Iraqi-Jewish
patients' platelets appeared to be slightly more severe. This finding
indicates that GPIIb/IIIa is the major determinant of platelet fibrinogen,
presumably acting by receptor- mediated uptake, and that the alpha v beta 3
vitronectin receptor plays little or no role. Arab patients' platelets have
normal amounts of platelet vitronectin, whereas Iraqi-Jewish patients'
platelets have nearly five times as much vitronectin as control or Arab
patients' platelets. To account for these data, we propose a working
hypothesis in which vitronectin is synthesized in megakaryocytes and the
alpha v beta 3 vitronectin receptor is involved in transport of the protein
out of megakaryocytes and/or platelets. Collectively, these observations
suggest that in addition to their recognized roles in cell adhesion and in
the interaction of cells with extracellular proteins, integrin receptors
may be important in protein trafficking into, and perhaps out of,
platelets.
Volume 78,
Issue 10,
pp. 2603-2610,
11/15/1991
Copyright © 1991 by The American Society of Hematology
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