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M Miura, CW Jackson and SA Lyles
To gain insight into the regulation of megakaryocyte precursors in vivo, we
assayed (in vitro) megakaryocyte growth-promoting activity (Meg-GPA) in
plasma of rats in which both marrow hypoplasia and thrombocytopenia had
been induced by irradiation. Rats received whole body irradiation of 834
rad from a 137Cs source. Plasma was collected at intervals of hours to
days, up through day 21 postirradiation, and was tested, at a concentration
of 30%, for Meg-GPA on bone marrow cells cultured in 1.1% methylcellulose
with 5 X 10(-5) M 2-mercaptoethanol. With normal rat plasma, no
megakaryocyte colonies (defined as greater than or equal to 4
megakaryocytes) were seen and only a few single megakaryocytes and clusters
(defined as 2 or 3 megakaryocytes) were formed. Two peaks of plasma Meg-GPA
were observed after irradiation. The first appeared at 12 hr, before any
decrease in marrow megakaryocyte concentration or platelet count. The
second occurred on days 10-14 after irradiation, after the nadir in
megakaryocyte concentration and while platelet counts were at their lowest
levels. A dose-response study of plasma concentration and megakaryocyte
growth, using plasma collected 11 days postirradiation, demonstrated that
patterns of megakaryocyte growth were related to plasma concentration;
formation of single megakaryocytes was optimal over a range of 20%-30%
plasma concentration, while cluster and colony formation were optimal at a
plasma concentration of 30%. All forms of megakaryocyte growth were
decreased with 40% plasma. There was a linear relationship between the
number of bone marrow cells plated and growth of single cells, clusters,
and colonies using a concentration of 30% plasma collected 11 days after
irradiation. We conclude that irradiation causes time- related increases in
circulating megakaryocyte growth-promoting activity. We suggest that the
irradiated rat is a good model for studying the relationships between
Meg-GPA and megakaryocyte and platelet concentration in vivo.
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| Copyright © 1984 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||