Disease relevance of GM-CSF

• Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) shortens the period of neutropenia after autologous bone marrow transplantation in a primate model [1].
• Expression of GM-CSF by the live attenuated recombinant virus did not per se affect the level of pulmonary viral replication in rhesus monkeys after topical administration, which was 40-fold lower than that of WT parainfluenza virus type 3 [2].
• GM-CSF effects on astrocytes could be involved in astrocytosis, a hallmark of various neurological injuries and in inflammatory processes in an autocrine manner [3].
• Here, we use a vaccine consisting of DNA priming followed by MVA boosting in rhesus macaques to investigate the ability of GM-CSF DNA to serve as an adjuvant for the elicitation of neutralizing Ab against an HIV-1 Env [4].
• Synergistic neutralizing antibody response to a dengue virus type 2 DNA vaccine by incorporation of lysosome-associated membrane protein sequences and use of plasmid expressing GM-CSF [5].

Psychiatry related information on GM-CSF

• The discordant results of this growth factor combination in these two models may imply codependence of the hematopoietic response to TPO and/or GM-CSF on other factors or cytokines [6].

High impact information on GM-CSF

• Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF [7].
• We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis [7].
• We conclude that GM-CSF may be useful in accelerating bone marrow reconstitution [1].
• After withdrawal of GM-CSF, neutrophil counts fell to values comparable to those observed in untreated controls [1].
• In addition, topical immunization with the attenuated virus expressing GM-CSF induced a greater number of virus-specific IFN-gamma-secreting T lymphocytes in the peripheral blood of monkeys than did immunization with the control virus bearing an unrelated RNA insert [2].

Biological context of GM-CSF

• The kinetics of the carbohydrate-specific IgG response correlated with a temporary release of cytokines such as IFNgamma, IL-2, IL-1beta, TNFalpha and GM-CSF which was measurable in the immune serum by xMAP Multiplex technology [8].
• In contrast, neither IL-3 alone nor simultaneously administered IL-3/GM-CSF elicited increases in thrombopoiesis between days 3 and 15 [9].
• Platelet counts maximally increased to a mean of 7.5 x 10(5)/microL (n = 3) on days 11 through 12 in monkeys treated with sequential IL-3/GM-CSF [9].
• Megakaryocyte ploidy distributions were significantly (P < .001) shifted between days 7 and 10 in monkeys treated sequentially and between days 3 and 15 in monkeys treated with combined IL-3/GM-CSF and with GM-CSF alone but not in monkeys treated with IL-3 alone [9].
• CD34+ cells with high GM-CSF-receptor expression coexpressed high levels of the class II major histocompatibility antigen RhLA-DR, whereas CD34+/RhLA-DRlow cells, which represent developmentally earlier cells, were either GM-CSF-receptor negative or expressed GM-CSF receptors at very low levels [10].

Anatomical context of GM-CSF

• Instead, GM-CSF stimulation resulted in terminal differentiation into adherent cells, showing that these cells represented monocyte precursors [10].
• We conclude that administration of IL-3 followed by GM-CSF treatment increases thrombopoiesis by sequentially increasing megakaryocyte numbers and maturation and that these effects are diminished by simultaneous administration of the two cytokines [9].
• The results show that GM-CSF-receptor expression is initiated in a subset of immature, CD34bright/RhLA-DRdull cells and is progressively increased during differentiation into mature granulocytes and monocytes [10].
• TPO/GM-CSF was more effective than single-dose TPO alone in stimulating thrombocyte regeneration, with a less profound nadir and a further accelerated recovery to normal thrombocyte counts, as well as a slight overshoot to supranormal levels of thrombocytes [11].
• Also, reticulocyte production was stimulated by TPO and further augmented in monkeys treated with TPO/GM-CSF [11].

Associations of GM-CSF with chemical compounds

• Sequential, overlapping infusions of IL-3 and GM-CSF produced a small but statistically significant increase in F-reticulocytes in one of two hydroxyurea-treated animals [12].
• Biotin-labeled granulocyte-macrophage colony-stimulating factor (GM-CSF), in combination with phycoerythrin-conjugated streptavidin, enabled flow cytometric analysis of specific cell-surface GM-CSF receptors on rhesus monkey bone marrow (BM) and peripheral blood (PB) cells [10].

Other interactions of GM-CSF

• A large fraction (> 30%) of single-cell/well-sorted CD34bright/RhLA-DRdull cells formed multilineage colonies after 2 to 4 weeks of stimulation with IL-3, GM-CSF, Kit ligand, and IL-6 [13].

Analytical, diagnostic and therapeutic context of GM-CSF

• Animals were given a continuous intravenous infusion of recombinant human GM-CSF for several days both before and after transplantation or only after the transplant procedure [1].
• Furthermore, we demonstrated that GM-CSF mediates its effect on these cells through the alpha subunit of the GM-CSF receptor which is constitutively expressed at the membrane of the cultured simian astrocytes as assessed by immunofluorescence [3].
• Microglial cells differed from macrophages by their proliferation upon granulocyte-macrophage colony stimulating factor (GM-CSF) treatment and by their typical morphology when observed by scanning electron microscopy [14].
• Controlled release of granulocyte-macrophage colony-stimulating factor (GM-CSF) protein by albumin-heparin microparticles administered via intramuscular vaccination in conjunction with HIV DNA vaccines stimulated HIV Gag-specific immune responses [15].
• Coadministration of pVecB7, a replication-defective SIV DNA vaccine, with interleukin-12 and GM-CSF expression plasmids, induced markedly enhanced control of viral replication and disease-free survival in macaques challenged intrarectally with pathogenic SIVsmE660 [16].

References