Cytokine Regulation of the Macrophage (M ) System Studied Using the Colony
Stimulating Factor-1-Deficient op/op Mouse.
Wiktor-Jedrzejczak, Wieslaw and Simon Gordon.
Dept. of Immunology, Central Clinical Hospital, Military School of
Medicine, Warsaw, Poland; and Sir William Dunn School og Pathology, University
of Oxford, Oxford, United Kingom.
APStracts 2:0037P, 1996.
ABSTRACT
The macrophage (M ) lineage is more complex than other myeloid lineages of
hematopoietic cells and includes strinkingly different end cells such as
Kupffer cells, alveolar M , histiocytes, serosal M , synovial type A cells,
microglia, osteoclasts, and possibly dendritic cells. These cells are formed
under the influence of primary M growth factors such as colony stimulating
factor (CSF)-1, granulocyte-M (GM)-CSF, and interleukin-3. The dissections
of the system has been greatly facilitated by discovery of the osteopetrotic
op/op mouse, which has a spontaneous knockout of the gene for CSF-1 and
possesses generalized but differntial deficiency of various local
subpopulations of M . Studies using this model indicate that the M lineage
is plit into CSF-1- dependent and CSF-1-independant cells that are largely
independently regulated. These contribute variably to differnt local
populations and have largely, but not totally, overlapping functins. Both
CSF-1 and FM-CSF are responsible for transition of cells of the M lineage
from bone marrow to blood, and from blod to tissues, and have a critical
extramedullary role. Regulation of the M system by CSF-1 is complex, with
some local populations dependent on circulating CSF-1 and some supported
exclusively by locally produced CSF-1. Colony stimulating factor-1-dependent
M are not required for the generation of a specific immune response.
Instead, most likel they play a regulatory role in various tissue reactions
including responses to bacterial infection, neoplasia, and atherosclerosis. A
hyothetical major role of CSF-1-independent M is to collaborate with
lumphocytes in mounting an immune response. These issues need further
exploration using animals with knockouts of genes for other M growth and
activation factors and their receptors.
APS Manuscript Number P11-6.
Article publication pending October 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996