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Cellular and Molecular Life Sciences :... Apr 2022Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent... (Review)
Review
Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent neuroinflammation is considered a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and primary progressive multiple sclerosis (MS). Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its expression is significantly increased in neurodegenerative diseases. Cumulative findings have indicated that CSF-1R inhibitors can have beneficial effects in preclinical neurodegenerative disease models. Research using CSF-1R inhibitors has now been extended into non-human primates and humans. This review article summarizes the most recent advances using CSF-1R inhibitors in different neurodegenerative conditions including AD, PD, HD, ALS and MS. Potential challenges for translating these findings into clinical practice are presented.
Topics: Alzheimer Disease; Animals; Colony-Stimulating Factors; Microglia; Neurodegenerative Diseases; Parkinson Disease
PubMed: 35366105
DOI: 10.1007/s00018-022-04225-1 -
Cancer Immunology Research Dec 2013The colony-stimulating factors (CSFs) are the master regulators of granulocyte and macrophage populations. There are four different aspects of the connection between the... (Review)
Review
The colony-stimulating factors (CSFs) are the master regulators of granulocyte and macrophage populations. There are four different aspects of the connection between the CSFs and cancer: (a) the CSFs can accelerate the regeneration of protective white cells damaged by chemotherapy; (b) the CSFs can mobilize stem cells to the peripheral blood in convenient numbers for transplantation; (c) the CSFs can enhance anticancer immune responses and (d) the CSFs are potentially involved in the genesis of the myeloid leukemias.
Topics: Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Neoplasms
PubMed: 24524092
DOI: 10.1158/2326-6066.CIR-13-0151 -
International Journal of Cell Cloning Jan 1987The granulocyte colony-stimulating factor (G-CSF) belongs to a family of hemopoietic growth factors regulating the production of granulocytes and macrophages. Murine... (Review)
Review
The granulocyte colony-stimulating factor (G-CSF) belongs to a family of hemopoietic growth factors regulating the production of granulocytes and macrophages. Murine G-CSF stimulates the proliferation and differentiation of precursors of neutrophilic granulocytes and is also able to stimulate the functional activities of mature neutrophils. Among the hemopoietic growth factors, G-CSF has an outstanding capacity to induce terminal differentiation and suppression of self-renewal in myeloid leukemic cells. Murine and human G-CSF's show complete biological cross-reactivity across species and bind equally well to G-CSF receptors of either species. Specific receptors for G-CSF exist on all normal neutrophilic cells and have not been lost in the generation of primary human myeloid leukemias. This data indicates that G-CSF may be a useful reagent in the treatment of myeloid leukemia, in hemopoietic regeneration and in increasing resistance against infections.
Topics: Amino Acid Sequence; Animals; Cell Differentiation; Cell Division; Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Growth Inhibitors; Growth Substances; Hematopoiesis; Humans; Interleukin-3; Interleukin-6; Leukemia Inhibitory Factor; Leukemia, Myeloid; Lymphokines; Mice; Neoplasm Proteins; Receptors, Cell Surface; Receptors, Colony-Stimulating Factor; Species Specificity
PubMed: 3031177
DOI: 10.1002/stem.5530050102 -
Seminars in Immunology Apr 2021Although traditionally seen as regulators of hematopoiesis, colony-stimulating factors (CSFs) have emerged as important players in the nervous system, both in health and... (Review)
Review
Although traditionally seen as regulators of hematopoiesis, colony-stimulating factors (CSFs) have emerged as important players in the nervous system, both in health and disease. This review summarizes the cellular sources, patterns of expression and physiological roles of the macrophage (CSF-1, IL-34), granulocyte-macrophage (GM-CSF) and granulocyte (G-CSF) colony stimulating factors within the nervous system, with a particular focus on their actions on microglia. CSF-1 and IL-34, via the CSF-1R, are required for the development, proliferation and maintenance of essentially all CNS microglia in a temporal and regional specific manner. In contrast, in steady state, GM-CSF and G-CSF are mainly involved in regulation of microglial function. The alterations in expression of these growth factors and their receptors, that have been reported in several neurological diseases, are described and the outcomes of their therapeutic targeting in mouse models and humans are discussed.
Topics: Animals; Colony-Stimulating Factors; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Humans; Macrophages; Mice; Microglia
PubMed: 34743926
DOI: 10.1016/j.smim.2021.101511 -
Neuroendocrinology 2021Stroke is a debilitating disease and has the ability to culminate in devastating clinical outcomes. Ischemic stroke followed by reperfusion entrains cerebral... (Review)
Review
Stroke is a debilitating disease and has the ability to culminate in devastating clinical outcomes. Ischemic stroke followed by reperfusion entrains cerebral ischemia/reperfusion (I/R) injury, which is a complex pathological process and is associated with serious clinical manifestations. Therefore, the development of a robust and effective poststroke therapy is crucial. Granulocyte colony-stimulating factor (GCSF) and erythropoietin (EPO), originally discovered as hematopoietic growth factors, are versatile and have transcended beyond their traditional role of orchestrating the proliferation, differentiation, and survival of hematopoietic progenitors to one that fosters brain protection/neuroregeneration. The clinical indication regarding GCSF and EPO as an auspicious therapeutic strategy is conferred in a plethora of illnesses, including anemia and neutropenia. EPO and GCSF alleviate cerebral I/R injury through a multitude of mechanisms, involving antiapoptotic, anti-inflammatory, antioxidant, neurogenic, and angiogenic effects. Despite bolstering evidence from preclinical studies, the multiple brain protective modalities of GCSF and EPO failed to translate in clinical trials and thereby raises several questions. The present review comprehensively compiles and discusses key findings from in vitro, in vivo, and clinical data pertaining to the administration of EPO, GCSF, and other drugs, which alter levels of colony-stimulating factor (CSF) in the brain following cerebral I/R injury, and elaborates on the contributing factors, which led to the lost in translation of CSFs from bench to bedside. Any controversial findings are discussed to enable a clear overview of the role of EPO and GCSF as robust and effective candidates for poststroke therapy.
Topics: Animals; Colony-Stimulating Factors; Erythropoietin; Humans; Ischemic Stroke; Reperfusion Injury
PubMed: 33075777
DOI: 10.1159/000512367 -
BMC Cancer Mar 2023Currently there are no established fertility preservation options for pre-pubertal boys facing cancer treatment. Granulocyte-colony stimulating factor (G-CSF) treatment...
BACKGROUND
Currently there are no established fertility preservation options for pre-pubertal boys facing cancer treatment. Granulocyte-colony stimulating factor (G-CSF) treatment has been proposed to be chemoprotective against spermatogonial cell loss in an alkylating chemotherapy model of busulfan treated adult mice. Having previously shown that exposure to the alkylating-like chemotherapy cisplatin resulted in a reduction in germ cell numbers in immature human testicular tissues, we here investigate whether G-CSF would prevent cisplatin-induced germ cell loss in immature human and mouse (fetal and pre-pubertal) testicular tissues.
METHODS
Organotypic in vitro culture systems were utilised to determine the effects of clinically-relevant concentrations of G-CSF in cisplatin-exposed immature testicular tissues. Human fetal (n = 14 fetuses) and mouse pre-pubertal (n = 4 litters) testicular tissue pieces were cultured and exposed to cisplatin or vehicle control for 24 hrs and analysed at 72 and 240 hrs post-exposure. Combined G-CSF and cisplatin exposure groups explored varying concentrations and duration of G-CSF supplementation to the culture medium (including groups receiving G-CSF before, during and after cisplatin exposure). In addition, effects of G-CSF supplementation alone were investigated. Survival of total germ cell and sub-populations were identified by expression of AP2γ and MAGE-A4 for human gonocytes and (pre)spermatogonia, respectively, and MVH and PLZF, for mouse germ cells and putative spermatogonial stem cells (SSCs) respectively, were quantified.
RESULTS
Exposure to cisplatin resulted in a reduced germ cell number in human fetal and mouse pre-pubertal testicular tissues at 240 hrs post-exposure. Germ cell number was not preserved by combined exposure with G-CSF using any of the exposure regimens (prior to, during or after cisplatin exposure). Continuous supplementation with G-CSF alone for 14 days did not change the germ cell composition in either human or mouse immature testicular tissues.
CONCLUSIONS
This study demonstrates that exposure to G-CSF does not prevent cisplatin-induced germ cell loss in immature human and mouse testicular tissues in an in vitro system.
Topics: Male; Humans; Animals; Mice; Testis; Cisplatin; Spermatogonia; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Granulocytes
PubMed: 36922758
DOI: 10.1186/s12885-023-10702-y -
Cytokine Jan 2024Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the... (Review)
Review
Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the bone marrow, which have been gaining attention for playing pro- and/or anti-tumorigenic roles in cancer. Head and neck cancers (HNCs) represent a group of heterogeneous neoplasms with high morbidity and mortality worldwide. Treatment for HNCs is still limited even with the advancements in cancer immunotherapy. Novel treatments for patients with recurrent and metastatic HNCs are urgently needed. This article provides an in-depth review of the role of hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3; also known as multi-CSF) in the HNCs tumor microenvironment. We have reviewed current results from clinical trials using CSFs as adjuvant therapy to treat HNCs patients, and also clinical findings reported to date on the therapeutic application of CSFs toxicities arising from chemoradiotherapy.
Topics: Humans; Colony-Stimulating Factors; Interleukin-3; Granulocyte Colony-Stimulating Factor; Cytokines; Granulocytes; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37944421
DOI: 10.1016/j.cyto.2023.156417 -
The Journal of Biological Chemistry Mar 1977Colony-stimulating factor, which specifically stimulates mouse bone marrow cells to proliferate in vitro and generate colonies of granulocytes, or macrophages, or both,...
Colony-stimulating factor, which specifically stimulates mouse bone marrow cells to proliferate in vitro and generate colonies of granulocytes, or macrophages, or both, was purified 3500-fold from mouse lung-conditioned medium. Analysis by discontinuous polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate indicated that there was a single protein component. All of the colony-stimulating activity was coincident with the protein band. The molecular weight of colony-stimulating factor estimated by gel filtration was approximately 29,000 and by electrophoresis approximately 23,000. The specific activity of purified colony-stimulating factor from mouse lung-conditioned medium bound to concanavalin A-Sapharose, indicating that it is a glycoprotein. The small percentage of colony-stimulating factor in mouse lung-conditioned medium which did not bind to concanavalin A-Sepharose appeared to represent molecules which lacked the carbohydrate moieties required for binding to this lectin. It was necessary to include low concentrations (less than 0.01%, v/v) of polymers such as gelatin and polyethylene glycol, or nonionic detergents such as Triton X-100, in all of the buffers used throughout the purification scheme, otherwise colony-stimulating factor was lost from solution. At high concentrations (greater than 20 mug/ml) the factor stimulated the formation of granulocytic, macrophage, and mixed colonies from C57BL mouse bone marrow cells. As the concentration of purified colony-stimulating factor was decreased, the frequency of colonies containing granulocytes also decreased. At low concentrations of colony-stimulating factor (less than 70 pg/ml) only macrophage colonies were stimulated.
Topics: Animals; Chromatography, Affinity; Colony-Stimulating Factors; Concanavalin A; Culture Media; Glycoproteins; Lung; Mice; Molecular Weight
PubMed: 300377
DOI: No ID Found -
The Journal of Experimental Medicine Nov 1987Hematopoietic cell development is regulated by a series of growth factors that are progressively restricted in their biological activity. IL-3 is a multi-lineage growth...
Hematopoietic cell development is regulated by a series of growth factors that are progressively restricted in their biological activity. IL-3 is a multi-lineage growth factor that supports the growth and differentiation of progenitor cells belonging to multiple lineages. However, the mechanism by which IL-3 induces proliferation and differentiation of these cells is not completely understood. In this report, we have used two IL-3-dependent cell lines, FDC-P1 (a myeloid progenitor) and F15.12 (a lymphoid progenitor) to investigate IL-3-mediated growth and differentiation. When either FDC-P1 or FL5.12 cells are deprived of IL-3, greater than 90% of all cells accumulate in the G0 phase of the cell cycle. Upon readdition of IL-3, the cells will reenter the active phases of the cell cycle. Therefore, IL-3 can act as both a competence (G0----G1) factor, and a progression (G1----M) factor for hematopoietic precursor clones. FDC-P1 cells can also proliferate in response to granulocyte/macrophage colony-stimulating factor (G/M-CSF) and IL-4 (B cell stimulatory factor 1 [BSF-1]). However, resting (G0) FDC-P1 cells have lost their ability to grow in response to both G/M-CSF and IL-4, even though both factors can induce a G0----G1 transition. Therefore, G/M-CSF or IL-4 behave as progression factors among certain IL-3-responsive clones, and in those cases only in defined points in the cell cycle. Both IL-4 and G/M-CSF can maintain long-term growth of FDC-P1 cells. Upon removal of factor for 24 h, these clones accumulate in the G1 phase of the cell cycle and do not appear to enter G0 even after 36 h of factor deprivation. Therefore, cells maintained in G/M-CSF or IL-4 have altered growth requirements compared with the IL-3-dependent lines from which they were derived. The ability of various hematopoietic growth factors to regulate cell cycle progression in IL-3-dependent cell lines is dependent not only upon the lineage from which these cells were derived, but also the phase of the cell cycle in which those cells reside. The consequences of these interactions dictate the manner by which various clones will respond to CSFs and whether the cells will grow and/or differentiate.
Topics: B-Lymphocytes; Cell Cycle; Cell Differentiation; Cell Division; Cell Line; Clone Cells; Colony-Stimulating Factors; DNA; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Growth Substances; Hematopoietic Stem Cells; Interleukin-3; Interleukin-4; Interleukins; Interphase; Kinetics
PubMed: 3316471
DOI: 10.1084/jem.166.5.1419 -
Journal of Clinical Oncology : Official... Mar 2012In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor...
PURPOSE
In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor (HR) -negative tumors, were reported. We examined first-cycle colony-stimulating factor use (FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy.
METHODS
We identified patients in Surveillance, Epidemiology, and End Results-Medicare greater than 65 years old with stages I to III breast cancer who had greater than one chemotherapy claim within 6 months of diagnosis(1998 to 2005) and classified patients with an average cycle length less than 21 days as having received dose-dense chemotherapy. The associations of patient, tumor, and physician-related factors with the receipt of any colony-stimulating factor (CSF) and FC-CSF use were analyzed by using generalized estimating equations. CSF costs were estimated for patients who were undergoing dose-dense chemotherapy.
RESULTS
Among the 10,773 patients identified, 5,266 patients (48.9%) had a CSF claim. CSF use was stable between 1998 and 2002 and increased from 36.8% to 73.7% between 2002 and 2005, FC-CSF use increased from 13.2% to 67.9%, and pegfilgrastim use increased from 4.1% to 83.6%. In a multivariable analysis, CSF use was associated with age and chemotherapy type and negatively associated with black/Hispanic race, rural residence, and shorter chemotherapy duration. FC-CSF use was associated with high socioeconomic status but not with age or race/ethnicity. The US annual CSF expenditure for women with HR-positive tumors treated with dose-dense chemotherapy is estimated to be $38.8 million.
CONCLUSION
A rapid increase in FC-CSF use occurred over a short period of time, which was likely a result of the reported benefits of dose-dense chemotherapy and the ease of pegfilgrastim administration. Because of the increasing evidence that elderly HR-positive patients do not benefit from dose-dense chemotherapy, limiting pegfilgrastim use would combat the increasing costs of cancer care.
Topics: Aged; Aged, 80 and over; Breast Neoplasms; Chemotherapy, Adjuvant; Colony-Stimulating Factors; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms, Hormone-Dependent; Polyethylene Glycols; Recombinant Proteins; SEER Program; Socioeconomic Factors; United States
PubMed: 22312106
DOI: 10.1200/JCO.2011.37.7499