Cytokine Regulation of the Macrophage M[stod]o System Studied Using the
Colony Stimulating Factor-1-Deficient [i]op/op[r] Mouse.
Wieslaw Wiktor-Jedrzejczak, and Siamon Gordon.
Dept. of Immunology, Central Clinical Hospital, Military School of
Medicine, Warsaw, Poland; and Sir William Dunn School of Pathology, University
of Oxford, Oxford, United Kingdom.
APStracts 2:0017P, 1996.
ABSTRACT
The macrophage (M[stod]o) lineage is more complex than other myeloid lineages
of hematopoietic cells and includes strikingly different end cells such as
Kupffer cells, alveolar M[stod]o, histiocytes, serosal M[stod]o, synovial type
A cells, microglia, osteoclasts, and possibly dendritic cells. These cells are
formed under the influence of primary M[stod]o growth factors such as colony
stimulating factor (CSF)-1, granulocyte-M[stod]o (GM)-CSF, and interleukin-3.
The dissection of the system has been greatly facilitated by discovery of the
osteopetrotic [i]op/op[r] mouse, which has a spontaneous knockout of the gene
for CSF-1 and possesses generalized but differential deficiency of various
local subpopulations of M[stod]o. Studies using this model indicate that the
M[stod]o lineage is split into CSF-1-dependent and CSF-1-independent cells
that are largely independently regulated. These contribute variably to
different local populations and have largely, but not totally, overlapping
functions. Both CSF-1 and GM-CSF are responsible for transition of cells of
the M[stod]o lineage from bone marrow to blood, and from blood to tissues, and
have a critical extramedullary role. Regulation of the M[stod]o 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[stod]o are not required for the generation of a specific
immune response. Instead, most likely they play a regulatory role in various
tissue reactions including responses to bacterial infection, neoplasia, and
atherosclerosis. A hypothetical major role of CSF-1-independent M[stod]o is to
collaborate with lymphocytes in mounting an immune response. These issues need
further exploration using animals with knockouts of genes for other M[stod]o
growth and activation factors and their receptors.
APS Manuscript Number P.
Article publication pending October 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996