Physiological Reviews, Vol 76, 927-947, Copyright © 1996 by American Physiological Society
Cytokine regulation of the macrophage (M phi) system studied using the colony stimulating factor-1-deficient op/op mouse
W. Wiktor-Jedrzejczak and S. Gordon
Department of Immunology, Military School of Medicine, Warsaw, Poland.
The macrophage (M phi) lineage is more complex than other myeloid lineages
of hematopoietic cells and includes strikingly different end cells such as
Kupffer cells, alveolar M phi, histiocytes, serosal M phi, synovial type A
cells, microglia, osteoclasts, and possibly dendritic cells. These cells
are formed under the influence of primary M phi growth factors such as
colony stimulating factor (CSF)-1, granulocyte-M phi (GM)-CSF, and
interleukin-3. The dissection 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 differential
deficiency of various local subpopulations of M phi. Studies using this
model indicate that the M phi 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 phi lineage from bone marrow to blood, and
from blood to tissues, and have a critical extramedullary role. Regulation
of the M phi 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 phi 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 phi is to collaborate with
lymphocytes in mounting an immune response. These issues need further
exploration using animals with knockouts of genes for other M phi growth
and activation factors and their receptors.
