Endocytosis of fibrinogen into hamster megakaryocyte alpha granules is
dependent on a dimeric gamma A configuration
PJ Handagama, DL Amrani and MA Shuman
Department of Pathology, University of California, San Francisco, USA.
Two species of fibrinogen that differ only in the structure of their gamma
chains, gamma A and gamma', are present in normal plasma. Fibrinogen stored
in platelet alpha granules does not contain gamma' chains. Because platelet
fibrinogen was recently shown to be derived exclusively by
receptor-mediated endocytosis from plasma and not by endogenous
megakaryocyte synthesis, we postulated that the gamma' fibrinogen present
in plasma is not endocytosed by megakaryocytes and platelets. We tested
this hypothesis by studying endocytosis of peak 1 (containing two gamma A
chains) and peak 2 (containing one gamma A and one gamma' chain) fractions
of human fibrinogen obtained from diethyl aminoethyl (DEAE) cellulose
chromatography in an in vivo hamster model. When 10 mg of biotinylated,
unfractionated, or peak 1 fibrinogen was injected intravenously, each
protein was endocytosed into megakaryocytes and platelets within 24 hours.
In contrast, equivalent doses of biotinylated peak 2 fibrinogen and bovine
serum albumin were barely detectable within megakaryocytes and platelets.
We conclude that gamma' fibrinogen is not endocytosed and incorporated into
megakaryocytes and platelet alpha granules. Furthermore, a dimeric gamma
A-chain configuration is required for receptor-mediated endocytosis of
fibrinogen into these organelles.
Volume 85,
Issue 7,
pp. 1790-1795,
04/01/1995
Copyright © 1995 by The American Society of Hematology
