Cataloguenumber
CYT-221
Synonyms
CSF-2,MGI-1GM,GM-CSF,Pluripoietin-alpha,MGC131935,MGC138897.
Introduction
GranulocyteMacrophageColonyStimulatingFactor(GM-CSF)wasfirstcharacterizedasagrowthfactorthatsupportsthein-vitrocolonyformationofgranulocytes-macrophagesProgenitorcells.Itisapleiotropiccytokineandamemberofafamilyofendogenouscytokinesofthehematopoieticsystem.GM-CSFisproducedasaresponsetoimmuneorinflammatorystimulibyactivatedcellsofthehematopoieticsystemsuchasTcells,Bcells,macrophages,mastcellsandalsofibroblastsandalveolarepithelialcells.Itplaysanimportantroleinregulatingtheproliferation,differentiation,survivalandactivationofhematopoieticcellssuchasgranulocytesandmonocytes,neutrophiles,basophilesandeosonophoiles,erythroidcells,megakaryocytesandTcells.
HumanandmouseGM-CSFhaveabout56%homologyandarespeciesspecific.HumanGM-CSFisnotactiveonmousecellsandviceversa.Itisactiveoncanineandfelinecells.
GMCSFis144aminoacids,22kDaglycoprotein.Itiscomposedoffourbundlesalphahelices.Itsreceptorisheterodimerswithaligand-specificalphasubunitandabetacsubunitthatissharedwiththeinterleukinIL-3andIL-5receptors.ThisunusualformofreceptorassemblylikelyappliesalsotoIL-3andIL-5receptors.Cross-linkingthetworeceptorsubunitsisrequiredforreceptoractivationandsignaling.
GMCSFhasbeenshowntobeinvolvedinmaturation,mobilizationandantigenpresentationofmyeloiddentriticcells(DCs)in-vivoorex-vivo.ThisfunctionpromotesTh1immuneresponses,cytotoxcity,anti-angiogenesisaswellasallergicinflammation,andthedevelopmentofautoimmunity.ThereforeGMCSFcanbeusedinimmunotherapyforthetreatmentofimmunesuppressedandimmune-compromisedpatientsaswellasinveterinarymedicineforthesamepurpose.GM-CSFisalsoimportantinregulationofembryodevelopmentandpregnancyandspecificallyinembryoimplantationandsubsequentdevelopment.
Description
Source
PhysicalAppearance
Formulation
Solubility
StABIlity
Forlongtermstorageitisrecommendedtoaddacarrierprotein(0.1%HSAorBSA).
Pleasepreventfreeze-thawcycles.
Purity
1.AnalysisbyRP-HPLC.
2.AnalysisbySDS-PAGE.
Aminoacidsequence
N-terminalmethioninehasbeencompletelyremovedenzymatically.
BIOLOGicalActivity
Proteincontent
1.UVspectroscopyat280nmusingtheabsorbencyvalueof0.963astheextinctioncoefficientfora0.1%(1mg/ml)solution.ThisvalueiscalculatedbythePCGENcomputeranalysisprogramofproteinsequences(IntelliGenetics).
2.AnalysisbyRP-HPLC,usingastandardsolutionofGM-CSFasaReferenceStandard.
Usage
Background
GM-CSFhassimilareffectstoG-CSFwhichiswidelyusedasatherapeuticagentinimmunosupressedpatientsmostlytoboostproductionofthemyeloidlineageafterchemotherapy-inducedneutropenia.UsingGM-CSFwasalsoshowntoboostanti-tumorimmunitybypromotingthematurationofantigenpresentingdendriticcells(DCs)andTh1responses.Itwassuggestedfortherapeuticusesinvariouscancersincludingfollicularlymphoma,acuteleukemiaandprostatecancer.GM-CSFisparticularaffectiveasanantitumorvaccinewhenusedintumorcellsengineeredtosecretGM-CSF.GM-CSFisalsoinvolvedinthetreatmentofCrohn"sdisease.AnotheruseofGM-CSFisasavaccineadjuvantanditwasalsoclaimedtoimprovethegeneralhealthconditionofAIDSpatientsalthoughthisisacontroversialissueanditwasrecentlyfoundthatGM-CSFactuallyinducestheexpressionofHIV-1inmonocytes. GM-CSFwasalsofoundtobeeffectiveandisusedinveterinarymedicine.
GM-CSFwasalsoshowntoplayapivotalroleinregulationofembryodevelopmentandpregnancyandparticularlyinembryoimplantationandplacentadevelopment.
AbnormalitiesinGM-CSFproductionorreceptorfunctionwereimplicatedindiseasessuchrheumatoidarthritis,juvenileandchronicmyelomonocyticleukemiaandalveolarproteinosisaswellasinthepathogenesisofmyeloproliferativediseases.