Biology Reference
In-Depth Information
The role of IGF-1 is unclear. In
in vitro
cell culture systems, IGF-1 can sub-
stitute for EPO, using a signaling pathway that appears to be independent of
EPO. It may serve as a substitute for EPO as the erythropoietic stimulus in
anephric patients who maintain a low but significant amount of erythropoiesis.
Erythroid cultures from patients with polycythemia vera are hyper-responsive
to IGF-1, suggesting it may have a role in the EPO-independent erythropoiesis
in this myeloproliferative disease [48, 49].
Apoptosis
A network of cytokines, including EPO, are required for normal growth and
differentiation of erythroid cells. The cytokines essential for the viability of
these cells inhibit apoptosis by augmenting the transcription of apoptosis-sup-
pressing genes such as bcl-2 and bcl-X
L
[50]. In contrast, inflammatory
cytokines such as tumor necrosis factor (TNF
) and interferon (IFN
)
can acti-
α
γ
γ
vate the death signal in erythroid progenitor cells through upregulation of the
FasL/Fas apoptotic pathway [51]. Binding of the FasL to Fas activates the pro-
teolytic caspases that cleave a number of intracellular proteins, including
GATA-1, with the subsequent loss of bcl-X
L
[52].
A second distinct Fas/FasL pathway is intrinsic to the erythroblast cell line.
Fas is present on both early and late erythroid precursors, but its activating lig-
and (FasL) appears only on late erythroblasts. The expression of FasL may
serve to regulate erythropoiesis within the erythropoietic islands of the bone
marrow as the mature erythroblasts expressing FasL induce apoptosis of their
Fas positive immature precursors [53].
Acknowledgements
The authors thank Marie Field for her secretarial expertise in the preparation of the manuscript.
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