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Granulocyte-macrophage colony-stimulating factor is not responsible for the
correction of hematopoietic deficiencies in the maturing op/op mouse
SK Nilsson, GJ Lieschke, CC Garcia-Wijnen, B Williams, D Tzelepis, G Hodgson, D Grail, AR Dunn and I Bertoncello
Sir Donald and Lady Trescowthick Research Laboratories, Peter MacCallum
Cancer Institute, Melbourne, Australia.
Osteopetrotic (op/op) mice are characterized by an autosomal recessive
inactivating mutation resulting in the absence of biologically active
colony-stimulating factor-1 (CSF-1). Consequently, young op/op mice have a
severe deficiency of macrophages and osteoclasts resulting in excessive
bone formation, occlusion of the marrow cavity, and reduced marrow
hematopoietic activity. Recently, we showed that the osteopetrosis and
hematopoietic deficiencies evident in young op/op mice are not permanent
but are progressively corrected with age. There are increases in osteoclast
activity; bone resorption; femoral marrow space; and marrow hematopoietic
activity, cellularity, and macrophage content. In the present study we show
that CSF-1-/- granulocyte- macrophage colony-stimulating factor
(GM-CSF)(-/-)-deficient mice also undergo the same pattern of hematopoietic
correction as the op/op mouse. Also, like the op/op mouse, the peritoneal
cellularity and macrophage content of CSF-1/GM-CSF-deficient mice remains
severely reduced. Our data show that the "knockout" of GM-CSF does not
change the op/op phenotype, and that GM-CSF is not essential for the
correction of the hematopoietic deficiencies in the op/op mouse.
Importantly, the data also show that neither GM-CSF nor CSF-1 is an
absolute requirement for the commitment of primitive hematopoietic stem
cells to the macrophage lineage or for the differentiation of at least some
classes of macrophages. This finding suggests that an alternate regulatory
factor can be involved in macrophage and osteoclast commitment,
differentiation, and function in vivo.
Volume 86,
Issue 1,
pp. 66-72,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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