Publication

Myeloperoxidase attracts neutrophils by physical forces

Klinke, A., Nussbaum, C., Kubala, L., Friedrichs, K., Rudolph, T. K., Rudolph, V., Paust, H-J., Schroeder, C., Benten, D., Lau, D., Szocs, K., Furtmueller, P. G., Heeringa, P., Sydow, K., Duchstein, H-J., Ehmke, H., Schumacher, U., Meinertz, T., Sperandio, M. & Baldus, S., 27-Jan-2011, In : Blood. 117, 4, p. 1350-1358 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Anna Klinke
  • Claudia Nussbaum
  • Lukas Kubala
  • Kai Friedrichs
  • Tanja K. Rudolph
  • Volker Rudolph
  • Hans-Joachim Paust
  • Christine Schroeder
  • Daniel Benten
  • Denise Lau
  • Katalin Szocs
  • Paul G. Furtmueller
  • Peter Heeringa
  • Karsten Sydow
  • Hans-Juergen Duchstein
  • Heimo Ehmke
  • Udo Schumacher
  • Thomas Meinertz
  • Markus Sperandio
  • Stephan Baldus

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. (Blood. 2011; 117(4):1350-1358)

Original languageEnglish
Pages (from-to)1350-1358
Number of pages9
JournalBlood
Volume117
Issue number4
Publication statusPublished - 27-Jan-2011

    Keywords

  • SURFACE-CHARGE, CHEMOTACTIC FACTORS, LEUKOCYTE ADHESION, ENDOTHELIAL-CELLS, INFLAMMATION, GLYCOCALYX, CD11B/CD18, PROTEINS, INCREASE, ALPHA(M)BETA(2)

View graph of relations

ID: 5254199