Targeting ADAM17 in leukocytes increases neutrophil recruitment and reduces bacterial spread during polymicrobial sepsis

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

关键词: inflammation;    microbiota;    TACE;   

DOI  :  10.1189/jlb.3VMAB1115-496RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Arapidandrobustrecruitmentofcirculatingneutrophilsatsitesofinfectioniscriticalforpreventingbacterialspread.Theefficiencyofthisprocess,however,isgreatlydiminishedduringsepsis,aseveresystemicinflammatoryresponsetoinfection.Theproteolyticactivityofadisintegrinandmetalloprotease‐17isinducedinthecellmembraneofleukocytesupontheiractivation,resultingintheconversionofmembranetosolubleTNF‐αandthereleaseofassortedreceptorsfromthesurfaceofneutrophilsimportantfortheireffectorfunctions.Weshowthatconditionalknockoutmicelackingadisintegrinandmetalloprotease‐17inallleukocyteshadasurvivaladvantagewhensubjectedtopolymicrobialsepsis.Bacteremiaandthelevelsofcirculatingproinflammatorycytokines,keydeterminantsofsepsisseverity,weresignificantlyreducedinconditionaladisintegrinandmetalloprotease‐17knockoutmiceduringsepsis.Althoughcecalbacterialmicrobiotaandloadweresimilarinunmanipulatedconditionaladisintegrinandmetalloprotease‐17knockoutandcontrolmice,peritonealspreadofbacteriawassignificantlyreducedinconditionaladisintegrinandmetalloprotease‐17knockoutmicefollowingsepsisinduction,whichwasassociatedwithanamplifiedrecruitmentofneutrophils.Takentogether,ourfindingssuggestthatextensiveadisintegrinandmetalloprotease‐17inductionduringsepsismaytipthebalancebetweenefficientandimpairedneutrophilrecruitment...

【 授权许可】

CC BY