Myeloperoxidase attracts neutrophils by physical forces.
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Myeloperoxidase attracts neutrophils by physical forces. / Klinke, Anna; Nussbaum, Claudia; Kubala, Lukas; Friedrichs, Kai; Rudolph, Tanja Katharina; Rudolph, Volker; Paust, Hans-Joachim; Schröder, Christine; Benten, Daniel; Lau, Denise; Szöcs, Katalin; Furtmüller, Paul G; Heeringa, Peter; Sydow, Karsten; Duchstein, Hans-Jürgen; Ehmke, Heimo; Schumacher, Udo; Meinertz, Thomas; Sperandio, Markus; Baldus, Stephan.
In: BLOOD, Vol. 117, No. 4, 4, 2011, p. 1350-1358.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Myeloperoxidase attracts neutrophils by physical forces.
AU - Klinke, Anna
AU - Nussbaum, Claudia
AU - Kubala, Lukas
AU - Friedrichs, Kai
AU - Rudolph, Tanja Katharina
AU - Rudolph, Volker
AU - Paust, Hans-Joachim
AU - Schröder, Christine
AU - Benten, Daniel
AU - Lau, Denise
AU - Szöcs, Katalin
AU - Furtmüller, Paul G
AU - Heeringa, Peter
AU - Sydow, Karsten
AU - Duchstein, Hans-Jürgen
AU - Ehmke, Heimo
AU - Schumacher, Udo
AU - Meinertz, Thomas
AU - Sperandio, Markus
AU - Baldus, Stephan
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2010-05-284513
DO - 10.1182/blood-2010-05-284513
M3 - SCORING: Journal article
VL - 117
SP - 1350
EP - 1358
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 4
M1 - 4
ER -