Myeloperoxidase attracts neutrophils by physical forces
| Autor: | Christine Schröder, Lukáš Kubala, Denise Lau, Markus Sperandio, Claudia Nussbaum, Tanja K. Rudolph, Stephan Baldus, Daniel Benten, Anna Klinke, Katalin Szöcs, Paul G. Furtmüller, Kai Friedrichs, Hans-Jürgen Duchstein, Peter Heeringa, Heimo Ehmke, Karsten Sydow, Udo Schumacher, Volker Rudolph, Thomas Meinertz, Hans-Joachim Paust |
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| Přispěvatelé: | Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR) |
| Rok vydání: | 2011 |
| Předmět: |
Male
Endothelium GLYCOCALYX PROTEINS Neutrophils Surface Properties Static Electricity Immunology LEUKOCYTE ADHESION Motility Inflammation Granulocyte Biochemistry INCREASE ALPHA(M)BETA(2) Physical Phenomena Glycocalyx Mice CHEMOTACTIC FACTORS INFLAMMATION medicine Animals Humans CD11B/CD18 Cells Cultured Peroxidase Mice Knockout biology Chemistry Chemotaxis Cell Biology Hematology ENDOTHELIAL-CELLS Extravasation Cell biology SURFACE-CHARGE Mice Inbred C57BL medicine.anatomical_structure Neutrophil Infiltration Myeloperoxidase biology.protein medicine.symptom Hydrophobic and Hydrophilic Interactions Protein Binding |
| Zdroj: | Blood, 117(4), 1350-1358. AMER SOC HEMATOLOGY |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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