title: Methods for measuring myeloperoxidase activity toward assessing inhibitor efficacy in living systems.
abstract: Myeloperoxidase aids in clearance of microbes by generation of peroxidase-mediated oxidants that kill leukocyte-engulfed pathogens. In this review, we will examine 1) strategies for in vitro evaluation of myeloperoxidase function and its inhibition, 2) ways to monitor generation of certain oxidant species during inflammation, and 3) how these methods can be used to approximate the total polymorphonuclear neutrophil chemotaxis following insult. Several optical imaging probes are designed to target reactive oxygen and nitrogen species during polymorphonuclear neutrophil inflammatory burst following injury. Here, we review the following 1) the broad effect of myeloperoxidase on normal physiology, 2) the difference between myeloperoxidase and other peroxidases, 3) the current optical probes available for use as surrogates for direct measures of myeloperoxidase-derived oxidants, and 4) the range of preclinical options for imaging myeloperoxidase accumulation at sites of inflammation in mice. We also stress the advantages and drawbacks of each of these methods, the pharmacokinetic considerations that may limit probe use to strictly cell cultures for some reactive oxygen and nitrogen species, rather than in vivo utility as indicators of myeloperoxidase function. Taken together, our review should shed light on the fundamental rational behind these techniques for measuring myeloperoxidase activity and polymorphonuclear neutrophil response after injury toward developing safe myeloperoxidase inhibitors as potential therapy for chronic obstructive pulmonary disease and rheumatoid arthritis.
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Huang
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Milton
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Arnold
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
authors.forename: Forrest
authors.initials: F
authors.lastname: Smith
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Panizzi
authors.affiliation: *Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA panizzi@auburn.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Panizzi
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D051379:Mice; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000032:analysis* / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009195:Peroxidase
keywords: bioluminescence; neutrophil chemotaxis; noninvasive imaging; reactive nitrogen species; reactive oxygen species