The hematopoietic growth factor, granulocyte macrophage colonystimulating factor gmcsf, is considered to play a central role in maintaining chronic inflammation. Autoimmune pulmonary alveolar proteinosis apap is a rare pulmonary disease caused by functional deficiency of granulocytemacrophage colonystimulating factor gmcsf. Granulocyte macrophage colonystimulating factoractivated. Administration of gmcsf represents a potential therapeutic strategy in management of apap. Mar 11, 2020 whereas the role played by cytokines as neuronal mediators is no longer contested, the mechanisms by which cytokines modulate pain processing remain to be elucidated. Granulocyte macrophage colony stimulating factor gm this work was supported by american cancer society research grant bc684, american cancer society jfra285 to j. The expression of granulocyte macrophage colony stimulating factor gmcsf and receptors in human endometrium. Wo2002069999a1 stable aqueous solutions of granulocyte. Granulocytemacrophage colonystimulating factor gmcsf and. Other haematopoietins may increase the number of circulating leucocytes with higher efficiency, but gmcsf has additional effects that may be far more relevant than its haematopoietic activity. Immunity article granulocyte macrophage colony stimulating factor activated eosinophils promote interleukin23 driven chronic colitis thibault griseri,1,2,6 isabelle c. Granulocyte colonystimulating factor and granulocyte.
For leucopenia to shorten time to white cell depletion recovery during chemotherapy, and to reduce the incidence of severe and lifethreatening infections. Yet, first data in head and neck squamous cell carcinoma hnscc indicate an impaired longterm prognosis on gcsf treatment, and previous studies showed a contribution of both factors to the progression of human. Other types of growth factors called granulocyte macrophage colony stimulating factors affect the growth of other types of white blood cells along with neutrophils. Effectiveness of granulocytemacrophage colonystimulating.
The pharmaceutical analogs of naturally occurring gmcsf are called sargramostim and molgramostim. The receptor is normally located on myeloblast, mature neutrophil, but not on any erythroid or megakaryocytic lineage cells. Granulocyte macrophagecolony stimulating factor gmcsf is a myelopoietic growth factor that has pleiotropic effects not only in promoting the differentiation of immature precursors into. A standard adjuvant approach has not been established.
In this study, we have analyzed the involvement of granulocyte macrophage colony stimulating factor gmcsf in nociceptor activation in male and female mice. Tnf and granulocyte macrophage colony stimulating factor gmcsf have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. Gmcsf induces differentiation, proliferation and activation of macrophages and dendritic cells which are. Granulocytemacrophage colonystimulating factor gmcsf was originally defined as a hemopoietic growth factor. Granulocytemacrophage colonystimulating factor gmcsf is known as an inducer of proliferation and.
Granulocytemacrophage colonystimulating factor gmcsf, also known as colony stimulating factor 2 csf2, is a monomeric glycoprotein secreted by macrophages, t cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The granulocytemacrophage colonystimulating factors science. Granulocyte macrophage colony stimulating factor expressed by recombinant respiratory syncytial virus attenuates viral replication and increases the level of pulmonary antigenpresenting cells. Eukaryotic cells also produce mcsf in order to combat intercellular viral infection. A laboratoryproduced version of this protein is often used to boost a low white blood cell count. Avian influenza has been widely spread all over the world, has caused property l. Granulocyte macrophage colony stimulating factor gmcsf is an important hematopoietic growth factor and immune modulator. Granulocyte colony stimulating factor gcsf gcsf is a type of growth factor. The present study was designed to investigate the previously unexplored role of gmcsf in. Granulocytemacrophage colonystimulating factor gmcsf is a colony stimulating factor approved by the fda for treatment of bone marrow transplant graft delay or failure and for speeding neutrophil recovery after induction chemotherapy in elderly patients with acute myelogenous leukemia. Involvement of granulocytemacrophage colonystimulating. Other haematopoietins may increase the number of circulating leucocytes with higher efficiency, but gmcsf has additional effects that may be far. Granulocyte macrophage colony stimulating factor gmcsf is a colony stimulating factor approved by the fda for treatment of bone marrow transplant graft delay or failure and for speeding neutrophil recovery after induction chemotherapy in elderly patients with acute myelogenous leukemia.
Arnold,1,2,6 claire pearson,1,2 thomas krausgruber,1,2 chris schiering,2,5. Granulocyte macrophage colony stimulating factor gmcsf is a naturally occurring cytokine that is involved in the normal maturation and functioning of alveolar macrophages, cells involved in host defense to infection, and inflammation. Tnf and granulocyte macrophagecolony stimulating factor. This model was utilized to demonstrate that the cytokine granulocyte macrophage colony stimulating factor gmcsf plays a critical and nonredundant role in mediating eae pathology, making it an ideal therapeutic target. Pdf receptors for granulocytemacrophage colonystimulating. Characterization of the soluble human granulocytemacrophage. Granulocytemacrophage colonystimulating factor receptor. This study shows the effect of gmcsf on mycobacterium avium complex mac infection in vivo using a c57bl6 beige mouse model of disseminated mac infection. May, 20 presentation on indications of granulocyte colony stimulating factors in chemotherapy induced neutr. Most of the red and white cells in the circulating blood are shortlived and need to be. Although steadystate hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and. This th2 pattern is associated with diminished ifn.
In conclusion, aerosolised granulocyte macrophage colony stimulating factor is safe and effective in treating pulmonary alveolar proteinosis providing an alternative to wholelung lavage or subcutaneous granulocyte macrophage colony stimulating factor. Granulocyte colony stimulating factor gcsf and granulocyte macrophage colony stimulating factor gmcsf are used to ameliorate cancer therapyinduced neutropenia and mucositis. It is one of the three experimentally described colony stimulating factors. Tnf and granulocyte macrophagecolony stimulating factor gmcsf have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. Granulocyte macrophage colony stimulating factor an overview. Local radiotherapy and granulocytemacrophage colony. Granulocytemacrophage colonystimulating factor definition. The granulocyte macrophage colony stimulating factor gmcsf is a hematopoietic colony stimulating factor and proinflammatory cytokine 11,43 with pleiotropic effects in innate and adaptive immunity. Csf on unresponsive thin granulocyte macrophage colony stimulating factor gmcsf and macrophage csf mcsf modulate differentiation and immune functions of macrophages m. The role of granulocytemacrophage colonystimulating factor.
Granulocyte macrophage colonystimulating factor journal of. Or you might have it before and after a stem cell transplant. Inhaled granulocytemacrophage colony stimulating factor for. Granulocyte macrophage colony stimulating factor gmcsf. Objective to assess the effect of granulocyte macrophage colony. Vaccination with irradiated tumor cells engineered to secrete murine granulocytemacrophage colonystimulating factor stimulates potent, specific, and longlasting antitumor immunity. Yet, first data in head and neck squamous cell carcinoma hnscc indicate an impaired longterm prognosis on gcsf treatment, and previous studies showed a. The effect of granulocytemacrophage colonystimulating factor gmcsf on hematopoietic reconstitution after autologous bone. Autoimmune pulmonary alveolar proteinosis apap is a rare pulmonary disease caused by functional deficiency of granulocyte macrophage colony stimulating factor gmcsf.
Granulocytemacrophage colonystimulating factor gmcsf is a colonystimulating factor approved by the fda for treatment of bone marrow transplant graft delay or failure and for speeding neutrophil recovery after induction chemotherapy in elderly patients with acute myelogenous leukemia. Surgical resection provides the only possibility of cure for pancreas cancer. Granulocyte macrophage colony stimulating factor, pulmonary alveolar proteinosis. The crystal structure of recombinant human granulocyte macrophage colony stimulating factor rhgmcsf has been refined against data extending to a resolution of approximately 2. To investigate the effects of gcsf or gmcsf therapy in nonneutropenic patients with sepsis. Like gp, gcsf receptor gcsfr is composed of six domains subdivided into an nterminal igd and five fniii domains that show an overall sequence homology of 46% 18. Granulocytemacrophage colony stimulating factor g0282. We report a case of exacerbated vasculitis in a patient with smallcell lung cancer who presented with a paraneoplastic vasculitis. Although lcs originate in bone marrow, little is known about their lineage of origin.
Granulocytemacrophage colony stimulating factordeficient mice show no major perturbation of hematopoiesis but. Granulocytemacrophage colonystimulating factor is a key. Pdf the expression of granulocyte macrophagecolony. This recombinant, human granulocytemacrophage colony stimulating factor gmcsf product is a 14. Although steadystate hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids. We tested the safety and efficacy of a granulocytemacrophage colonystimulating factor gmcsf based immunotherapy administered in patients with resected pancreatic adenocarcinoma. The role of granulocytemacrophage colonystimulating. Despite the fact that granulocyte macrophage colony stimulating factor gmcsf and granulocyte colony stimulating factor gcsf are increasingly used in clinical practice, little is known of.
Granulocyte macrophagecolony stimulating factor gmcsf. Previously we described an interleukin23 il23 granulocyte macrophage colony stimulating factor gmcsf axis as a key driver of dysregulated hematopoiesis in colitis griseri et al. Pdf granulocyte macrophagecolony stimulating factor gm. Granulocyte macrophage colonystimulating factor, gmcsf. Granulocytemacrophage colonystimulating factordeficient. Oct 01, 2001 the hematopoietic growth factor, granulocyte macrophage colony stimulating factor gmcsf, is considered to play a central role in maintaining chronic inflammation. Granulocytemacrophage colony stimulating factor, human. This product does not contain any hazardous materials with occupational exposure limits established by the region specific regulatory bodies.
Granulocytemacrophage colonystimulating factor gmcsf is an important hematopoietic growth factor and immune modulator. Pcr analysis showed that the basal expression of siglec. Whereas the role played by cytokines as neuronal mediators is no longer contested, the mechanisms by which cytokines modulate pain processing remain to be elucidated. Granulocyte macrophage colony stimulating factor an.
Granulocyte macrophagecolony stimulating factor gmcsf also has proinflammatory activity and there are promising signs that its blockade and that of its receptor are effective in ra trials, as well as in preclinical models 2 4. Granulocytemacrophage colonystimulating factor induces cytokine. Aerosol granulocytemacrophage colony stimulating factor for. Granulocytemacrophage colonystimulating factordeficient mice show no major perturbation of hematopoiesis but. Summary langerhans cells lcs are dendritic cells dcs that are present in the epidermis, bronchi, and mucosae. Relationship between diffuse pulmonary fibrosis, alveolar. Pdf granulocytemacrophage colonystimulating factor. The hematopoietic growth factor granulocyte macrophage colony stimulating factor gmcsf induces enhanced proliferation of progenitor cells and improves the function of antigenpresenting cells. Gmcsf is a secreted glycoprotein that regulates and promotes cellular growth and proliferation of the. Csf on unresponsive thin granulocyte macrophage colony stimulating factor gmcsf, also known as colony stimulating factor 2 csf2, is a monomeric glycoprotein secreted by macrophages, t cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. Granulocytemacrophage colony stimulating factor as an. Granulocyte colonystimulating factor gcsf and granulocyte macrophage colonystimulating factor gmcsf are used to ameliorate cancer therapyinduced neutropenia and mucositis.
Recombinant granulocyte macrophage colony stimulating factor rgmcsf is now being widely used in clinical trials. Granulocyte colonystimulating factor is a cytokine of the longchain, class i type that is a growth factor for the differentiation and maturation of neutrophilic granulocytes. Granulocyte macrophage colonystimulating factor an. We have determined the threedimensional structure of recombinant human granulocytecolonystimulating factor by xray crystallography. Granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor exacerbate atherosclerosis in apolipoprotein edeficient mice. Pdf pharmacokinetics of human granulocytemacrophage. Recombinant granulocytemacrophage colonystimulating. Pdf granulocytemacrophage colonystimulating factor gmcsf is an important hematopoietic growth factor and immune modulator. Eligible studies were randomized control trials rcts that compared granulocyte colony stimulating factor gcsf or granulocyte macrophage colony. Gmcsf also has profound effects on the functional activities of various. You might have gcsf after chemotherapy to help your white blood cells recover after treatment.
Pdf transforming growth factor b 1, in the presence of. Reported toxic effects include fever, nausea and vomiting, bone pain, and fluid retention 1, 2. Proteogenomic analysis of granulocyte macrophage colony. We previously identified a new gmcsfjmjd3 demethylaseinterferon regulatory factor 4 irf4ccl17 pathway that is active in monocytesmacrophages in vitro and important. However, it can act on mature myeloid cells 2 and it has other functions, acting as a proinflammatory cytokine 2 5 and in dendritic cell function 6. Granulocytemacrophage colonystimulating factor gmcsf is often used to treat leucopenia. Recombinant human granulocytemacrophage colonystimulating. Granulocytecolony stimulating factor gcsf critical care. 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. Granulocytemacrophage colonystimulating factor gmcsf. Granulocyte colony stimulating factor causes cells from the bone marrow to become mature and activated. The objective of the present study was to determine how neutrophil apoptosis was attenuated.
Pharmacokinetics of human granulocytemacrophage colonystimulating factor using a sensitive immunoassay article pdf available in blood 724. Pdf granulocyte macrophagecolony stimulating factor. In this study, we first analyzed granulocyte macrophage colony stimulating factor gmcsf autoantibodies in a patient with autoimmune pulmonary. Toxoplasma gondii induces granulocyte colonystimulating. A lethally irradiated allogeneic granulocytemacrophage.
The present study was designed to investigate the previously unexplored role of gmcsf in autoimmunemediated demyelination. Oct 01, 2001 granulocyte macrophage colony stimulating factor gmcsf is a myelopoietic growth factor that has pleiotropic effects not only in promoting the differentiation of immature precursors into. A systematic literature search of medline, embase and cochrane central register of controlled trials was conducted using specific search terms. Granulocytemacrophage colonystimulating factor gmcsf and t. One activator of macrophages is granulocyte macrophagecolony stimulating factor gmcsf whose tolllike receptor activation includes phagocytosis, bactericidal activity, oxidative burst, and cell adhesion in macrophages 5. Nov 22, 20 granulocytemacrophage colonystimulating factor gmcsf is often used to treat leucopenia. Granulocyte macrophage colony stimulating factor page 2 of 3 08 exposure controls personal protection control parameters exposure limits.
A complementary dna for the t lymphocytederived lymphokine, granulocyte macrophage colony stimulating factor gmcsf, has been cloned, and. Pulmonary alveolar proteinosis is an autoimmune disorder caused by a dysfunction in surfactant catabolism due to the disruption of granulocyte macrophage colony stimulating factor gmcsf signaling in relationship to the presence of autoantibodies that neutralize gmcsf. Previous studies have shown that recombinant granulocyte macrophage colony stimulating factor gmcsf stimulates human and murine macrophages to inhibit growth and kill intracellularly. Mar 18, 2020 in this study, we first analyzed granulocyte macrophage colony stimulating factor gmcsf autoantibodies in a patient with autoimmune pulmonary alveolar proteinosis, using the trapped ion. It is lyophilized from a 10 mm sodium citrate solution, ph 3. We report that this attenuation is mediated by both granulocyte colony stimulating factor gcsf and granulocyte macrophage colony stimulating factor gmcsf secreted by toxoplasmainfected fibroblasts. Sep 24, 2001 the hematopoietic growth factor, granulocyte macrophage colony stimulating factor gmcsf, is considered to play a central role in maintaining chronic inflammation. Bry k, hallman m, teramo k, waffarn f, lappalainen u 1997 granulocyte macrophage colony stimulating factor in amniotic.
Whitehead institute for biomedical research, massachusetts institute of technology, cambridge 02142. The crystal structure of recombinant human granulocyte macrophage colony stimulating factor rhgmcsf has been determined at 2. Monocytes are a subpopulation of peripheral blood leukocytes, which when appropriately activated by the regulatory hormones of the immune system, are capable of becoming macrophagespotent effector cells for immune response to tumors and parasites. We postulated that the exploitation of the proimmunogenic effects of radiotherapy with granulocyte macrophage colony stimulating factor might result in abscopal responses among patients with metastatic cancer. Gmcsf product description four distinct colonystimulating factors csfs that promote survival,proliferation, and differentiation of bone marrow precursor cells have been well. This recombinant, human granulocyte macrophage colony stimulating factor gmcsf product is a 14.
Eligible studies were randomized control trials rcts that compared granulocytecolony stimulating factor gcsf or granulocyte macrophage colony. Coadministration of an antigen and a granulocyte macrophage colony stimulating factor gmcsf hydrogel delivery system will afford a novel strategy for enhancement of an immune response because of the dual role of the hydrogel as a vaccine carrier with a sustained release and a platform for recruiting dendritic cells dcs. The granulocyte macrophage colony stimulating factor receptor also known as cd116 cluster of differentiation 116, is a receptor for granulocyte macrophage colony stimulating factor, which stimulates the production of white blood cells. Gmcsf is a growth factor secreted by several cell types from the innate immune system and functions as a cytokine stimulating the proliferation and differentiation of granulocytes, a class of white blood cells, mounting fast inflammatory response. One of the most wellstudied models of ms is experimental autoimmune encephalomyelitis eae. Granulocytecolony stimulating factor infectious diseases. The in vivo function of murine granulocyte macrophage colony stimulating factor gmcsf was investigated in mice, carrying a null allele of the gmcsf gene, that were generated by gene targeting techniques in embryonic stem cells.
There are two molecules in the crystallographic asymmetric unit, which are related by an approximate noncrystallographic 2fold axis. Granulocytemacrophage colony stimulating factor, from mouse recombinant, expressed in e. Apr 03, 2020 granulocyte macrophage colony stimulating factor speaker a protein that stimulates white blood cells, especially granulocytes, macrophages, and cells that become platelets, to multiply and mature. Asano s, sato n, mori m, ohsawa n, kosaka n, ueyama y 1980 detection and assessment of human granulocyte macrophage colony stimulating factor gmcsf producing tumors by heterotransplantation into nude mice. Granulocyte macrophage colony stimulating factor is a potent stimulator of dendritic cell maturation. Abstract avian influenza is an acute and highly contagious infectious disease that is caused by the influenza virus. Granulocyte macrophage colony stimulating factor, gmcsf sargramostim, leukine uses.
Pdf granulocyte macrophage colonystimulating factor. Its biological effects follow binding to the cell surface receptor granulocyte macrophage colony stimulating factor receptor. Studies in animals have shown increased antibody titer responses after vaccination in combination with gmcsf 12. Pdf granulocytemacrophage colonystimulating factor gmcsf. Granulocytemacrophage colonystimulating factor wikipedia. Injectable hydrogels coencapsulating granulocytemacrophage.