MACROPHAGE CONTROL OF NORMAL AND LEUKEMIC ERYTHROPOIESIS

Project Details

Description

The goal of this study is to define the role of macrophages in the
regulation of erythropoiesis. Macrophages directly influence the
growth and development of erythroid progenitors, both in vitro
and in vivo. Using a unique model system developed in our
laboratory, we have found that macrophage regulation of
erythropoiesis is impaired in erythroleukemia. This regulation can
be restored and the disease reversed by treatment with normal
macrophages.

The mechanism by which macrophages regulate normal and
leukemic erythropoiesis has been investigated. We have found
that there is a regulatory network operative in vivo involving
macrophages and erythroid progenitors (CFU-E), and potent
positive and negative regulatory mediators. Macrophages produce
a factor that greatly reduces in vivo CFU-E levels. This effect of
macrophages is reversed by an erythroid stimulatory activity,
related to but distinct from erythropoietin, induced by anemic
stress and whose activity in vivo is controlled by macrophages.

The aims of this study are to isolate and characterize these
erythroid regulatory activities; to determine their origins and
mechanisms of action; to assess their roles in controlling normal
and leukemic erythropoiesis; and to determine the interactions
between hematopoietic controls and immune functions known to
be involved in spontaneous and induced regression of
erythroleukemia, in reversal of the disease.

These findings reveal a novel and significant in vivo regulatory
circuit for the erythroid compartment, responsive to external
stimuli and tightly controlled by positive and negative mediators.
The systems we have developed uniquely allow analysis of this
regulatory axis, both in vitro and in vivo. Our studies offer the
possibility of gaining a greater understanding of erythropoiesis
and ultimately a potential for use of this knowledge in the therapy
of hematopoietic disorders.
StatusFinished
Effective start/end date12/31/891/1/90

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

ASJC

  • Cancer Research

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