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Granules of Platelets1
Department of Growth and Development, Davies Medical Center, San Francisco, California 94114
Address all correspondence and requests for reprints to: Kam Chan, Ph.D., Davies Medical Center, Laboratory of Growth and Development, Room B-200, Castro and Duboce Streets, San Francisco, California 94114. E-mail: igf{at}itsa.ucsf.edu
Lysis of platelets releases the contents of the 
-granules, which
contain growth factors, including insulin-like growth factor I (IGF-I)
and IGF-binding protein-3 (IGFBP-3). We investigated the mechanism by
which IGF-I and IGFBP-3 appeared in the -granules with a goal of
modulating their levels in platelets to affect platelet functions.
Reverse transcription-PCR was initially used to test whether
megakaryocytes contained IGFBP-3 and IGF-I messenger RNA transcripts.
We found that megakaryocytes did not express the IGFBP-3 gene, but did
have IGF-I messenger RNA. We subsequently investigated whether they
incorporated IGFBP-3 and IGF-I by the process of endocytosis and
packaged them into the -granules. This hypothesis was tested in two
ways. 1) We examined whether during pregnancy in the rat the
-granule content for IGFBP-3 paralleled the changes in plasma
IGFBP-3 levels caused by the pregnancy-induced IGFBP-3 protease. The
-granule contents of both IGFBP-3 and IGF-I declined in parallel to
the plasma changes in pregnant rats and returned to normal postpartum.
As the binding protein protease acts extracellularly, endocytosis of
the IGF-I:IGFBP-3 complex from the extracellular fluid by
megakaryocytes was suggested. 2) We tested whether an IGF-I:IGFBP-3
complex comprised of human IGF-I and IGFBP-3 (recombinant 28.7 kDa)
injected iv appeared in rat platelet -granules. Hypophysectomized
rats were injected iv with 5.24 mg of a 1:1 complex of IGF-I:IGFBP-3.
After 24 h, platelet lysates were prepared and analyzed for
IGFBP-3 by Western ligand blotting, and IGF-I was determined by RIA.
Platelet lysates of the treated animals showed a prominent new band at
approximately 28 kDa, whereas control rats were negative. In addition,
the -granule IGF-I concentration increased from 0.38 to 1.9
ng/1 x 109 platelets.
These results indicate that the IGF-I:IGFBP-3 complex is taken up by
megakaryocytes and packaged into the -granules of platelets and
demonstrate how the contents of IGF-I and IGFBP-3 in platelets can be
modulated by their plasma concentrations. As reverse transcription-PCR
has shown that the IGF-I, but not the IGFBP-3, gene is expressed by
megakaryocytes, there may be two mechanisms for directing IGF-I into
the -granules of platelets.
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