Myeloperoxidase attracts neutrophils by physical forces.
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.
Klinke
Anna
A
Department of Cardiology, University Heart Center, Martinistrasse 52, Hamburg, Germany.
Nussbaum
Claudia
C
Kubala
Lukas
L
Friedrichs
Kai
K
Rudolph
Tanja K
TK
Rudolph
Volker
V
Paust
Hans-Joachim
HJ
Schröder
Christine
C
Benten
Daniel
D
Lau
Denise
D
Szocs
Katalin
K
Furtmüller
Paul G
PG
Heeringa
Peter
P
Sydow
Karsten
K
Duchstein
Hans-Jürgen
HJ
Ehmke
Heimo
H
Schumacher
Udo
U
Meinertz
Thomas
T
Sperandio
Markus
M
Baldus
Stephan
S
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
D009195:Peroxidase