Granulocyte-macrophage colony-stimulating factor is not responsible for the correction of hematopoietic deficiencies in the maturing op/op mouse.
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.
Nilsson
S K
SK
Sir Donald and Lady Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, Australia.
Lieschke
G J
GJ
Garcia-Wijnen
C C
CC
Williams
B
B
Tzelepis
D
D
Hodgson
G
G
Grail
D
D
Dunn
A R
AR
Bertoncello
I
I
D000367:Age Factors; D000818:Animals; D001773:Blood Cells / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006411:Hematopoiesis, Extramedullary; D016130:Immunophenotyping; D016131:Lymphocyte Subsets; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains / Q000502:physiology*; D010022:Osteopetrosis / Q000235:genetics / Q000503:physiopathology*; D013154:Spleen / Q000473:pathology
D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor