title: Myeloperoxidase attracts neutrophils by physical forces.
abstract: Recruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are well characterized, receptor-mediated processes, mechanisms attenuating the electrostatic repulsion between the negatively charged glycocalyx of leukocyte and endothelium remain poorly understood. We provide evidence for myeloperoxidase (MPO), an abundant PMN-derived heme protein, facilitating PMN recruitment by its positive surface charge. In vitro, MPO evoked highly directed PMN motility, which was solely dependent on electrostatic interactions with the leukocyte's surface. In vivo, PMN recruitment was shown to be MPO-dependent in a model of hepatic ischemia and reperfusion, upon intraportal delivery of MPO and in the cremaster muscle exposed to local inflammation or to intraarterial MPO application. Given MPO's affinity to both the endothelial and the leukocyte's surface, MPO evolves as a mediator of PMN recruitment because of its positive surface charge. This electrostatic MPO effect not only displays a so far unrecognized, catalysis-independent function of the enzyme, but also highlights a principal mechanism of PMN attraction driven by physical forces.
authors.affiliation: Department of Cardiology, University Heart Center, Martinistrasse 52, Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Klinke
authors.forename: Claudia
authors.initials: C
authors.lastname: Nussbaum
authors.forename: Lukas
authors.initials: L
authors.lastname: Kubala
authors.forename: Kai
authors.initials: K
authors.lastname: Friedrichs
authors.forename: Tanja K
authors.initials: TK
authors.lastname: Rudolph
authors.forename: Volker
authors.initials: V
authors.lastname: Rudolph
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.forename: Christine
authors.initials: C
authors.lastname: Schröder
authors.forename: Daniel
authors.initials: D
authors.lastname: Benten
authors.forename: Denise
authors.initials: D
authors.lastname: Lau
authors.forename: Katalin
authors.initials: K
authors.lastname: Szocs
authors.forename: Paul G
authors.initials: PG
authors.lastname: Furtmüller
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Karsten
authors.initials: K
authors.lastname: Sydow
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Duchstein
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Thomas
authors.initials: T
authors.lastname: Meinertz
authors.forename: Markus
authors.initials: M
authors.lastname: Sperandio
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009195:Peroxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055585:Physical Phenomena; D011485:Protein Binding / Q000502:physiology; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D009195:Peroxidase