Methods for measuring myeloperoxidase activity toward assessing inhibitor efficacy in living systems

[摘要] Myeloperoxidaseaidsinclearanceofmicrobesbygenerationofperoxidase‐mediatedoxidantsthatkillleukocyte‐engulfedpathogens.Inthisreview,wewillexamine1)strategiesforinvitroevaluationofmyeloperoxidasefunctionanditsinhibition,2)waystomonitorgenerationofcertainoxidantspeciesduringinflammation,and3)howthesemethodscanbeusedtoapproximatethetotalpolymorphonuclearneutrophilchemotaxisfollowinginsult.Severalopticalimagingprobesaredesignedtotargetreactiveoxygenandnitrogenspeciesduringpolymorphonuclearneutrophilinflammatoryburstfollowinginjury.Here,wereviewthefollowing1)thebroadeffectofmyeloperoxidaseonnormalphysiology,2)thedifferencebetweenmyeloperoxidaseandotherperoxidases,3)thecurrentopticalprobesavailableforuseassurrogatesfordirectmeasuresofmyeloperoxidase‐derivedoxidants,and4)therangeofpreclinicaloptionsforimagingmyeloperoxidaseaccumulationatsitesofinflammationinmice.Wealsostresstheadvantagesanddrawbacksofeachofthesemethods,thepharmacokineticconsiderationsthatmaylimitprobeusetostrictlycellculturesforsomereactiveoxygenandnitrogenspecies,ratherthaninvivoutilityasindicatorsofmyeloperoxidasefunction.Takentogether,ourreviewshouldshedlightonthefundamentalrationalbehindthesetechniquesformeasuringmyeloperoxidaseactivityandpolymorphonuclearneutrophilresponseafterinjurytowarddevelopingsafemyeloperoxidaseinhibitorsaspotentialtherapyforchronicobstructivepulmonarydiseaseandrheumatoidarthritis...

[学科分类] 生理学

[关键词] bioluminescence;noninvasive imaging;neutrophil chemotaxis;reactive oxygen species;reactive nitrogen species