Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present in vitro study revealed marked differences in immunophenotypic expression and ultrastructure among macrophage colony-stimulating factor (M-CSF)-derived, granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived, and multi-CSF-derived macrophages. M-CSF-derived macrophages were larger and had more markedly differentiated intracellular organelles and more cytoplasmic projections than GM-CSF-or multi-CSF-derived macrophages. By the combined method of ultrastructural peroxidase cytochemistry and immunoelectron microscopy, ER-MP12 was demonstrated mainly on blastic cells; ER-MP20 on promonocytes, monocytes, and immature macrophages; and F4/80 or BM8 on immature and mature macrophages and monocytes. Macrophage heterogeneity was demonstrated to occur at the stage of macrophage precursor cells, and macrophage differentiation was different between bone marrow hematopoiesis and early fetal hematopoiesis. In vivo, F4/80- or BM8-positive (+) macrophages and ER-MP12 (+) cells developed in the yolk sac prior to the appearance of ER-MP20 (+) monocytic cell series. These results imply that CSFs are important factors for the generation of phenotypic heterogeneity of macrophage populations not only in bone marrow but also in fetal hematopoiesis, suggesting that there are different pathways of macrophage differentiation.
...
PMID:Immunophenotypic and ultrastructural heterogeneity of macrophage differentiation in bone marrow and fetal hematopoiesis of mouse in vitro and in vivo. 818 42

Mice homozygous for the disruption of the PU.1 (Spi-1) gene do not produce mature macrophages. In determining the role of PU.1 in macrophage differentiation, the present study investigated whether or not there was commitment to the monocytic lineage in the absence of PU.1. Early PU.1-/- myeloid colonies were generated from neonate liver under conditions that promote primarily macrophage and granulocyte/macrophage colonies. These PU.1-/- colonies were found to contain cells with monocytic characteristics as determined by nonspecific esterase stain and the use of monoclonal antibodies that recognize early monocyte precursors, including Moma-2, ER-MP12, ER-MP20, and ER-MP58. In addition, early myeloid cells could be grown from PU.1-/- fetal liver cultures in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Similar to the PU.1 null colonies, the GM-CSF-dependent cells also possessed early monocytic characteristics, including the ability to phagocytize latex beads. The ability of PU.1-/- progenitors to commit to the monocytic lineage was also verified in vivo by flow cytometry and cytochemical analysis of primary neonate liver cells. The combined data shows that PU.1 is absolutely required for macrophage development after commitment to this lineage.
...
PMID:Commitment to the monocytic lineage occurs in the absence of the transcription factor PU.1. 1021 79

Apoptotic death of CD8(+) T cells can be induced by a population of inhibitory myeloid cells that are double positive for the CD11b and Gr-1 markers. These cells are responsible for the immunosuppression observed in pathologies as dissimilar as tumor growth and overwhelming infections, or after immunization with viruses. The appearance of a CD11b(+)/Gr-1(+) population of inhibitory macrophages (iMacs) could be attributed to high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vivo. Deletion of iMacs in vitro or in vivo reversed the depression of CD8(+) T-cell function. We isolated iMacs from the spleens of immunocompromised mice and found that these cells were positive for CD31, ER-MP20 (Ly-6C), and ER-MP58, markers characteristic of granulocyte/monocyte precursors. Importantly, although iMacs retained their inhibitory properties when cultured in vitro in standard medium, suppressive functions could be modulated by cytokine exposure. Whereas culture with the cytokine interleukin 4 (IL-4) increased iMac inhibitory activity, these cells could be differentiated into a nonadherent population of fully mature and highly activated dendritic cells when cultured in the presence of IL-4 and GM-CSF. A common CD31(+)/CD11b(+)/Gr-1(+) progenitor can thus give rise to cells capable of either activating or inhibiting the function of CD8(+) T lymphocytes, depending on the cytokine milieu that prevails during antigen-presenting cell maturation. (Blood. 2000;96:3838-3846)
...
PMID:Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. 1109 68