Serum amyloid A1α induces paracrine IL‐8/CXCL8 via TLR2 and directly synergizes with this chemokine via CXCR2 and formyl peptide receptor 2 to recruit neutrophils

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

关键词: chemotaxis;    G protein‐;    coupled receptor;    chemoattractants;   

DOI  :  10.1189/jlb.3A0315-085R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Cellmigrationdependsontheabilityofleukocytestosenseanexternalgradientofchemotacticproteinsproducedduringinflammation.Theseproteinsincludechemokines,complementfactors,andsomeacutephaseproteins,suchasserumamyloidA.SerumamyloidAchemoattractsneutrophils,monocytes,andTlymphocytesviaitsGprotein‐coupledreceptorformylpeptidereceptor2.WedemonstratethatserumamyloidA1αmorepotentlychemoattractsneutrophilsinvivothaninvitro.IncontrasttoCD14+monocytes,norapid(within2h)inductionofinterleukin‐8/CXCchemokineligand8ormacrophage‐inflammatoryprotein‐1α/CCchemokineligand3wasobservedinpurifiedhumanneutrophilsafterstimulationofthecellswithserumamyloidA1αorlipopolysaccharide.Moreover,interleukin‐8/CXCchemokineligand8inductioninmonocytesbyserumamyloidA1αwasmediatedbytoll‐likereceptor2andwasinhibitedbyassociationofserumamyloidA1αwithhighdensitylipoprotein.ThisindicatesthatthepotentchemotacticresponseofneutrophilstowardintraperitoneallyinjectedserumamyloidA1αisindirectlyenhancedbyrapidinductionofchemokinesinperitonealcells,synergizinginaparacrinemannerwithserumamyloidA1α.WeobserveddirectsynergybetweenIL‐8/CXCchemokineligand8andserumamyloidA1α,butnotlipopolysaccharide,inchemotaxisandshapechangeassayswithneutrophils.Furthermore,theselectiveCXCchemokinereceptor2andformylpeptidereceptor2antagonists,SB225002andWRW4,respectively,blockedthesynergybetweenIL‐8/CXCchemokineligand8andserumamyloidA1αinneutrophilchemotaxisinvitro,indicatingthatforsynergytheircorrespondingGprotein‐coupledreceptorsarerequired.Additionally,SB225002significantlyinhibitedserumamyloidA1α‐mediatedperitonealneutrophilinflux.Takentogether,endogenous(e.g.,IL‐1β)andexogenous(e.g.,lipopolysaccharide)inflammatorymediatorsinduceprimarychemoattractantssuchasserumamyloidAthatsynergizeinanautocrine(monocyte)oraparacrine(neutrophil)fashionwithsecondarychemokinesinducedinstromalcells...

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