title: Mice lacking three myeloid colony-stimulating factors (G-CSF, GM-CSF, and M-CSF) still produce macrophages and granulocytes and mount an inflammatory response in a sterile model of peritonitis.
abstract: To assess the combined role of G-CSF, GM-CSF, and M-CSF in myeloid cell production, mice deficient in all three myeloid CSFs were generated (G-/-GM-/-M-/- mice). G-/-GM-/-M-/- mice share characteristics found in mice lacking individual cytokines: they are toothless and osteopetrotic and furthermore acquire alveolar proteinosis that is more severe than that found in either GM-/- or G-/-GM-/- mice. G-/-GM-/-M-/- mice have a significantly reduced lifespan, which is prolonged by antibiotic administration, suggesting compromised ability to control bacterial infection. G-/-GM-/-M-/- mice have circulating neutrophils and monocytes, albeit at significantly reduced numbers compared with wild-type mice, but surprisingly, have more circulating monocytes than M-/- mice and more circulating neutrophils than G-/-GM-/- mice. Due to severe osteopetrosis, G-/-GM-/-M-/- mice show diminished numbers of myeloid cells, myeloid progenitors, and B lymphocytes in the bone marrow, but have significantly enhanced compensatory splenic hemopoiesis. Although G-/-GM-/-M-/- mice have a profound deficiency of myeloid cells in the resting peritoneal cavity, the animals mount a moderate cellular response in a model of sterile peritonitis. These data establish that in the absence of G-CSF, GM-CSF, and M-CSF, additional growth factor(s) can stimulate myelopoiesis and acute inflammatory responses.
authors.affiliation: Signal Transduction Laboratory, Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, and Department of Medicine, University of Melbourne, Parkville, Australia. Margaret.Hibbs@ludwig.edu.au
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Hibbs
authors.forename: Cathy
authors.initials: C
authors.lastname: Quilici
authors.forename: Nicole
authors.initials: N
authors.lastname: Kountouri
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Jane E
authors.initials: JE
authors.lastname: Armes
authors.forename: Antony W
authors.initials: AW
authors.lastname: Burgess
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Dunn
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003115:Colony-Stimulating Factors / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology; D007970:Leukopenia / Q000235:genetics / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
chemical_list: D003115:Colony-Stimulating Factors; D018836:Inflammation Mediators; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor