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Macrophage‐colony stimulating factor is required for the production of neutrophil‐promoting activity by mouse embryo fibroblasts deficient in G‐CSF and GM‐CSF
Author(s) -
Zhang Hui Hua,
Basu Sunanda,
Wu Fenqiang,
Begley C. Glenn,
Saris Christiaan J. M.,
Dunn Ashley R.,
Burgess Antony W.,
Walker Francesca
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0107023
Subject(s) - neutrophilia , biology , colony stimulating factor , granulopoiesis , stimulation , macrophage colony stimulating factor , granulocyte macrophage colony stimulating factor , granulocyte , granulocyte colony stimulating factor , immunology , bone marrow , candida albicans , macrophage , in vitro , cytokine , microbiology and biotechnology , haematopoiesis , endocrinology , stem cell , biochemistry , genetics , chemotherapy
G‐CSF and GM‐CSF play important roles in regulating neutrophil production, survival, differentiation, and function. However, we have shown previously that G‐CSF/GM‐CSF double‐deficient [knockout (KO)] mice still develop a profound neutrophilia in bone marrow and blood after infection with Candida albicans . This finding suggests the existence of other systems, which can regulate emergency neutrophil production. We have now developed an “in vitro” technique to detect and characterize a neutrophil‐promoting activity (NPA) in the media conditioned by mouse embryonic fibroblasts (MEFs) derived from G‐CSF −/− /GM‐CSF −/− mice. NPA is produced in vitro by the MEFs after stimulation with LPS or heat‐inactivated C. albicans . Although M‐CSF added directly to bone marrow cultures does not sustain granulocyte production, our studies indicate that production of NPA requires activation of the M‐CSF receptor (c‐fms). First, G‐CSF −/− /GM‐CSF −/− MEFs produce high levels of NPA after stimulation with LPS or C. albicans , and G‐CSF/GM‐CSF/M‐CSF triple‐KO MEFs do not. Second, the production of NPA by the G‐CSF −/− /GM‐CSF −/− MEFs is reduced significantly upon incubation with neutralizing antibodies to M‐CSF or c‐fms. Third, NPA production by G‐CSF −/− /GM‐CSF −/− /M‐CSF −/− fibroblasts is enhanced by supplementing culture medium with M‐CSF. Thus, stimulation of c‐fms by M‐CSF is a prerequisite for the production of NPA.