It is one of the three experimentally described colonystimulating. These lecture notes accompany my lectures on pathophysiology in the study module musculoskeletal system at the medical university of innsbruck. Airway epithelial cellderived colony stimulating factor1. Colony stimulating factor1 plays a role in osteoclast. Pth stimulates osteoblasts to secrete il1, il6 and other cytokines to activate osteoclasts and increase resorption of bone. Increases osteoblast production of mcsf macrophage colony stimulating factor and rankl, which increases number of osteoclasts. Effect of granulocyte colonystimulating factor on bone metabolism during peripheral blood stem cell mobilization article pdf available in international journal of hematology 771. Hematology questions and study guide quizlet flashcards. Role of colony stimulating factor1 in brain damage caused by. Granulocytemacrophage colonystimulating factor upregulates. In addition, they find widespread depletion of microglia in csf1rhaploinsufficient zebrafish and leukodystrophy patients, also in the absence of pathology, indicating that microglia depletion may contribute to loss of white matter. Mcsf macrophage colonystimulating factor, csfr colony.
Felix r 1, hofstetter w, wetterwald a, cecchini mg, fleisch h. For initiation of experiments, fresh or frozen monocytes are cultured in flasks for 1 week with. Granulocytemacrophage colonystimulating factor receptor. Colony stimulating factor 1 csf 1 is a cytokine required for proliferation, differentiation, activity, and survival of cells of the. Microglia are the only type of brain cells expressing the colonystimulating factor 1 receptor, a key regulator for myeloid lineage cells. How diverse stimuli control hemopoietic lineage development is unknown.
Role of colony stimulating factor1 in brain damage caused. Nov 14, 2017 only one of the two forms of colonystimulating factor 1 csf1 plays a role in estrogendeficiency bone loss. Mar 15, 2006 we investigated bone gene expression in vivo during rapid osteoclast differentiation induced by colonystimulating factor 1 csf1 in csf1null toothless tltl rats. Colonystimulating factor1 csf1, released by osteoblasts, stimulates the proliferation of osteoclast progenitors via the cfms receptor csf1r and, in combination with receptor activator of nuclear factor. Role of colonystimulating factor1 in bone metabolism. Colony stimulating factor 1 receptor inhibition eliminates. Uses for sargramostim autologous and allogeneic bone marrow transplantation. Ligand binding activates the receptor kinase through a process of oligomerization and transphosphorylation. Colony stimulating factor 1 plays a role in osteoclast formation and function in bone resorption induced by parathyroid hormone and parathyroid hormonerelated protein. Granulocyte colonystimulating factor gcsf is the most commonly used cytokine for. Osteoblasts derived from opop mice do not support osteoclast development in vitro, while exogenous csf1 induces. Altered bone and mineral metabolism in patients receiving. Targeted overexpression of the two colonystimulating. Jun 28, 2019 colony stimulating factors csf are intriguing molecules, which are glycoproteins that control the production and even some functions of granulocytes and macrophages, the immune cells that are.
B ligand rankl, leads to the formation of mature osteoclasts. Increases osteoblast production of mcsf macrophage colonystimulating factor and rankl, which increases number of osteoclasts. We thus further investigated the effects of gcsf on ischemiainduced no production and its consequence on regional cerebral blood flow rcbf and neurological deficit. Colonystimulating factor1 csf1, also known as macrophagecsf mcsf, and its receptor csf1r, which is almost exclusively expressed by myeloid lineage cells, regulate the survival, proliferation, differentiation, and chemotaxis of tissue macrophages and dendritic cells, that play a key role in innate immune responses. Granulocyte colonystimulating factor gcsf has been shown to affect the biochemical markers of bone metabolism, including serum bone alkaline phosphatase balp, serum osteocalcin, and urine deoxypyridinoline. Mar 31, 2016 anti colony stimulating factor 1 receptor anticsfr1 antibody reduces the production of inflammatory mediators in synovial tissue in rheumatoid arthritis ra. Dec 03, 2018 the granulocyte colony stimulating factor gcsf is the most commonly used hematopoietic growth factor recombinant dna technology. The critical role of mcsf in osteoclast biology was established in a series of experiments on opop osteopetrosis mice. Osteoclasts are unique cells that degrade the bone matrix. In addition to il 1 and tnf, the spectrum of cytokines with effects on bone metabolism now includes the antiosteoclastogenic cytokines il4 and il10 and transforming growth factor tgf, and. The granulocyte colonystimulating factor gcsf is the most commonly used hematopoietic growth factor recombinant dna technology. Granulocytemonocyte colonystimulating factor gmcsf. Longbone rna from csf1treated tltl rats was analyzed by highdensity microarray over a time course. A protocol is presented for cell culture of macrophage colonystimulating factor mcsf differentiated human monocytederived macrophages.
Colonystimulating factor1 csf1 is essential for macrophage growth, differentiation and survival. Felix r1, hofstetter w, wetterwald a, cecchini mg, fleisch h. The specific functions of these forms are not clear. Impaired bone resorption in opop mice is associated with a marked reduction in the. These large multinucleated cells differentiate from the monocytemacrophage lineage upon stimulation by two essential cytokines, macrophage colonystimulating factor mcsf and receptor activator of nuclear factorkappa b nf. Colonystimulating factor csf 1 receptor blockade reduces. Macrophage colony stimulating factor csf1 is a critical growth factor for macrophage. However, the precise role of each form in osteoclastogenesis is unclear. Receptor, macrophage colony stimulating factor metabolism. To investigate the role of recombinant human macrophage colonystimulating factor rhmcsf on in vitro bone resorption, two bone explants, each at a different developmental stage, were adopted, namely 1 radii and 2 metatarsals of 17dayold embryonic mice. B ligand rankl and 30 ngml macrophage colonystimulating factor mcsf for 4 days in the presence of the vehicle 0. Macrophage colony stimulating factor receptor cfms is a novel target of imatinib.
Granulocytecolony stimulating factor increases cerebral. Role of osteopontin in bone remodeling and orthodontic. This receptor mediates most if not all of the biological effects of this cytokine. Agranulocytosis is the most serious side effect of antithyroid drug atd therapy. Jan 23, 20 bone marrow modulators, such as colonystimulating factors csfs and erythrocytestimulating agents esas, are used to treat toxicities of cancer chemotherapy. Colony stimulating factor 1 an overview sciencedirect. Bone marrow modulators, such as colonystimulating factors csfs and erythrocytestimulating agents esas, are used to treat toxicities of cancer chemotherapy.
Csf macrophage colony stimulating factor with rankl explained in the following section on parathyroid hormone, two cytokines produced by osteoblasts. Functions of the mcsf receptor on osteoclasts sciencedirect. Clinical studies reporting the use of gh and igf1 in osteoporosis and fracture healing are outlined. The colony stimulating factor 1 csf1, also known as macrophage colonystimulating factor mcsf, is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. The protein encoded by this gene is the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. Granulocytemacrophage colony stimulating factor gmcsf is a cytokine produced predominantly by activated t lymphocytes. The survival of microglia depends on colony stimulating factor 1 receptor csf1r signaling. Osteoclastmediated bone resorption is stimulated during short. The growth factor is synthesized as a soluble, matrix, or membrane associated molecule. Although colony stimulating factor 1 csf 1 plays a key role in osteoclast recruitment, studies examining the effect of csf 1 on mature osteoclasts indicate that it may directly inhibit bone. Here, we determined the effects of a colonystimulating factor 1 receptor.
Trap tartrateresistant acid phosphatasepositive osteoclasts. A marked effect of colony stimulating factor1csf1 on microglial response and neuron survival in cerebral cortex ischemic damage was obwerved. Colonystimulating factor1 stimulates the fusion process in. Rescue of the osteopetrotic defect in opop mice by osteoblastspecific targeting of soluble colony stimulating factor 1. The effects of shortterm use of granulocyte colony. A role for cellsurface csf1 in osteoblastmediated osteoclastogenesis. Selective deletion of the soluble colonystimulating. Local factors regulating bone metabolism 1 factors stimulating osteoblast differentiation.
Effect of granulocyte colonystimulating factor on bone metabolism during peripheral blood stem cell mobilization article pdf available in international journal of hematology 77 1. The role of t lymphocytes in bone metabolism request pdf. Colonystimulating factor 1 receptor csf1r regulates. Pdf effect of granulocyte colonystimulating factor on bone.
Eukaryotic cells also produce mcsf in order to combat intercellular viral infection. Microglia are the first responders to intracerebral hemorrhage, but their precise role in intracerebral hemorrhage remains to be defined. Induction by both tumor necrosis factoralpha and interleukin 1, downregulation by transforming growth factor beta and upregulation by fibroblast growth factor. Anticolony stimulating factor1 receptor anticsfr1 antibody reduces the production of inflammatory mediators in synovial tissue in rheumatoid arthritis ra. Effect of ghigf1 on bone metabolism and osteoporsosis. Effect of granulocyte colonystimulating factor on bone. Csf, is a heavily glycosylated cytokine that exists in two forms, soluble and membrane. Osteoclast function depends on polarization of the cell, induced by integrin. Metabolism of bone and its remodeling functions of cells. B family of signaling molecules in bone metabolism was evident. In this study, we show that 1 125ilabeled mcsf ligand specifically binds to the mcsf.
We investigated bone gene expression in vivo during rapid osteoclast differentiation induced by colonystimulating factor 1 csf1 in csf1null toothless tltl rats. Colonystimulating factor1 csf1, also called macrophage colonystimulating factor. Targeted overexpression of the two colonystimulating factor. Cecchini mg 1, hofstetter w, halasy j, wetterwald a, felix r. Pth stimulates osteoblasts to secrete il 1, il6 and other cytokines to activate osteoclasts and increase resorption of bone. Growth hormone gh and insulinlike growth factor igf1 are fundamental in skeletal growth during puberty and bone health throughout life.
Regulation of granulocyte macrophage colony stimulating factor production by human articular chondrocytes. The soluble form is derived from a 554 amino acid precursor that yields, following processing, subunits of 223 amino acids which form homodimers. For initiation of experiments, fresh or frozen monocytes are cultured in flasks for 1 week with mcsf to induce their differentiation into macrophages. Colony stimulating factor 1 receptor csf1r, also known as macrophage colonystimulating factor receptor mcsfr, and cd115 cluster of differentiation 115, is a cellsurface protein encoded, in humans, by the csf1r gene known also as cfms. We conducted prospective and randomized studies to examine whether granulocyte colonystimulating factor gcsf is actually effective for atdinduced agranulocytosis. Induction by both tumor necrosis factor alpha and interleukin 1, downregulation by transforming growth factor beta and upregulation by fibroblast growth factor. The critical role of the colonystimulating factor1. Granulocytemacrophage colonystimulating factor gmcsf is a cytokine produced predominantly by activated t lymphocytes. It is a receptor for a cytokine called colony stimulating factor 1.
An early event during induction of macrophage differentiation in the myeloblastic leukemia m1 cell line by different stimuli, such as leukemia inhibitory factor lif and interleukin6 il6, is expression of the colony stimulating factor 1 receptor csf1r. Detection of transcripts and binding sites for colonystimulating factor1. Bone is a highly dynamic tissue that undergoes continuous remodeling, which is regulated by various factors, including cytokineschemokines, hormones, and mechanical stimuli. Tnf and granulocyte macrophagecolony stimulating factor. Alsalameh s, firestein gs, oez s, kurrle r, kalden jr, burmester gr. It affects bone metabolism by modulating both osteoclast and osteoblast functions. Pamidronate 3amino1hydroxypropylidene1,1bisphosphonate was. Biosynthetic hematopoietic agent that affects the proliferation and differentiation of a variety of hematopoietic progenitor cells.
Macrophage colonystimulating factor m csf receptor has been previously reported to be present. Rescue of the osteopetrotic defect in opop mice by osteoblastspecific targeting of soluble colonystimulating factor1. Granulocyte colonystimulating factor gcsf does not. The role of macrophage stimulating factor mcsf in bone resorption.
Macrophage colonystimulating factor receptor cfms is a novel target of imatinib. Gh increases tissue formation by acting directly and indirectly on target cells. An early event during induction of macrophage differentiation in the myeloblastic leukemia m1 cell line by different stimuli, such as leukemia inhibitory factor lif and interleukin6 il6, is expression of the colonystimulating factor1 receptor csf1r. Rescue of the osteopetrotic defect in opop mice by osteoblast. Colony stimulating factor 1 receptor csf1r, also known as macrophage colony stimulating factor receptor mcsfr, and cd115 cluster of differentiation 115, is a cellsurface protein encoded, in humans, by the csf1r gene known also as cfms. Csf1, a protein responsible for white cell proliferation, is required for the. A protocol is presented for cell culture of macrophage colony stimulating factor mcsf differentiated human monocytederived macrophages. Pdf effect of granulocyte colonystimulating factor on. Recombinant human interleukin 1 alpha and beta stimulate mouse osteoblast like cells mc3t3e1 to produce macrophagecolony stimulating activity and. To determine the association between bone resorption and formation and the gcsfinduced mobilization of peripheral blood stem cells pbsc, we examined these markers during. Please vote below and help us build the most advanced adaptive. In addition to il1 and tnf, the spectrum of cytokines with effects on bone metabolism now includes the antiosteoclastogenic cytokines il4 and il.
Granulocytecolony stimulating factor gcsf protects brain from ischemicreperfusion ir injury, and inhibition of nitric oxide no synthases partially reduces gcsf protection. The critical role of the colonystimulating factor1 receptor. Chemokine and chemokine receptor expression during colony. Opop mice are devoid of serum and tissue csf1 activity and have an osteopetrotic phenotype due to a lack of osteoclasts 17, 26, 27. To determine the association between bone resorption and formation and the gcsfinduced mobilization of peripheral blood stem cells. Effect of granulocyte colonystimulating factor on bone metabolism during peripheral blood stem cell mobilization article pdf available in international journal. Osteoblasts and stromal cells are the main source of csf1 in the bone. However, there is limited information on gmcsfr expression in human central nervous system cns, peripheral nerves, or dorsal root ganglia drg, particularly in chronic. Role of colony stimulating factor1 in brain damage caused by ischemia. The colony stimulating factor 1 csf1, also known as macrophage colony stimulating factor mcsf, is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types.
In osteopetrotic opop mice, which lack systemically. The cell surface form of colonystimulating factor1 is biologically active in bone in vivo. The impact of the granulocyte colonystimulating factor on chemotherapy dose intensity and cancer survival. Only one of the two forms of colonystimulating factor 1 csf1 plays a role in estrogendeficiency bone loss. In addition, mediators produced by macrophages and other cells during inflammatory responses enhance osteoclast differentiation. Soluble colonystimulating factor1 scsf1 and membrane bound csf1 are. Granulocytemacrophage colonystimulating factor receptor gmcsfr is highly expressed in peripheral macrophages and microglia, and is involved in arthritis and cancer pain in animal models. A schematic representation of bone resorption occurring at cellular and molecular level. A bone marrowderived macrophages bmms were cultured with 10 ngml receptor activator of nuclear factor. Selective deletion of the soluble colonystimulating factor 1. Colonystimulating factors for febrile neutropenia during cancer therapy.
635 127 1286 1163 990 553 538 1514 884 566 733 393 525 642 1065 1304 817 521 904 804 605 926 269 508 32 347 1210 1173 717 1090