The innate defense regulator peptides IDR‐HH2, IDR‐1002, and IDR‐1018 modulate human neutrophil functions

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: cell activation;    chemotaxis;    host defense peptide;    immunomodulation;   

DOI  :  10.1189/jlb.1012497

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AlthoughHDPswereoriginallyhypothesizedtoactasantimicrobialagents,theyalsohavebeenshowntobroadlymodulatetheimmuneresponsethroughtheactivationofdifferentcelltypes.Werecentlydevelopedaseriesofnovel,syntheticpeptides,termedIDRs,whichareconceptuallybasedonanaturalHDP,bovinebactenecin.WeshowedthatIDR‐1andIDR‐1002protectthehostagainstbacterialinfectionsthroughtheinductionofchemokines.TheobjectiveofthisstudywastoinvestigatetheeffectsoftheIDRsonvariousfunctionsofhumanneutrophils.Here,wedemonstratedthatIDR‐HH2,IDR‐1002,andIDR‐1018modulatedtheexpressionofneutrophiladhesionandactivationmarkers.Moreover,theseIDRsenhancedneutrophiladhesiontoendothelialcellsinaβ2integrin‐dependentmannerandinducedneutrophilmigrationandchemokineproduction.TheIDRpeptidesalsoincreasedthereleaseoftheneutrophil‐generatedHDPs(antimicrobial),humanα‐defensins,andLL‐37andaugmentedneutrophil‐mediatedkillingofEscherichiacoli.Notably,theIDRssignificantlysuppressedLPS‐mediatedneutrophildegranulation,thereleaseofROS,andtheproductionoftheinflammatorycytokinesTNF‐αandIL‐10,consistentwiththeirabilitytodampeninflammation.AsevidencedbytheinhibitoryeffectsofMAPK‐specificinhibitors,IDRsactivatedtheMAPKpathwaythatwasrequiredforchemokineproduction.Inconclusion,ourstudyprovidesnovelevidenceregardingthecontributionoftheIDRpeptidestotheinnateimmuneresponsethroughthemodulationofneutrophilfunctions.TheresultsdescribedheremayaidinthedevelopmentofIDRsasnovel,anti‐infectiveandimmunomodulatoryagents...

【 授权许可】

CC BY