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  • 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.
    Author: Hibbs ML, Quilici C, Kountouri N, Seymour JF, Armes JE, Burgess AW, Dunn AR.
    Journal: J Immunol; 2007 May 15; 178(10):6435-43. PubMed ID: 17475873.
    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.
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