Inflammation‐dependent α5β1 (very late antigen‐5) expression on leukocytes reveals a functional role for this integrin in acute peritonitis

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

关键词: recruitment;    adhesion molecule;    VLA‐;    5;    fibronectin;    intravital microscopy;    cell adhesion;   

DOI  :  10.1189/jlb.1009670

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Thepotentialroleofα5β1(VLA‐5)inleukocytetraffickinginzymosan‐inducedacuteperitonitiswasdetermined.Innaïvemice,∼98%ofGr1highcells(PMN)inbonemarrowandcirculationwereα5β1‐negative;theseprofilesweremodestlyaffectedbyperitonealinjectionofzymosan.Incontrast,∼30%ofGr1highcellsrecruitedbyzymosan(24h)totheperitonealcavityexpressedα5β1.WithrespecttoF4/80+cells,∼60%ofbonemarrowandperipheralbloodpopulationsexpressedα5β1,with∼90%positivityinresidentcellsofnoninflamedperitoneum.Analysisofα5β1expressionrevealedinflammation‐dependentincreasedexpressiononGr1highandF4/80+cellsinbonemarrow,blood,andperitonealcavity.Blockadeofα5β1,byananti‐α5mAb,attenuatedzymosan‐induced24hrecruitmentofGr1highandF4/80+cells.Atleastoneunderlyingmechanismofthisactionwasreductionofcelladhesionandtransmigrationacrossmicrovascularvessels,asrevealedbyintravitalmicroscopy.Confocalanalysesindicatedthatdepositionoffibronectin,theprincipalligandforα5β1,wasup‐regulatedsignificantlyonandaroundtheinflamedmesentericmicrovasculature.Thesedatasuggestthattheeffectsofα5‐blockademaybearesultofinhibitionofα5β1‐dependentleukocyteadhesiontoandmigrationalongthefibronectinmatrix.Thisisthefirstreportthatidentifiesafunctionalroleforα5β1inleukocytetraffickingduringacuteinflammation...

【 授权许可】

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