Activated factor XI inhibits chemotaxis of polymorphonuclear leukocytes

Asako Itakura, Norah G. Verbout, Kevin G. Phillips, Robert H. Insall, David Gailani, Erik I. Tucker, Andras Gruber, Owen J.T. McCarty

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

PMN leukocytes are the most abundant leukocytes in the circulation and play an important role in host defense. PMN leukocyte recruitment and inflammatory responses at sites of infection are critical components in innate immunity. Although inflammation and coagulation are known to have bidirectional relationships, little is known about the interaction between PMN leukocytes and coagulation factors. Coagulation FXI participates in the intrinsic coagulation pathway upon its activation, contributing to hemostasis and thrombosis. We have shown previously that FXI-deficient mice have an increased survival and less leukocyte accumulation into the peritoneum in severe polymicrobial peritonitis. This result suggests a role for FXI in leukocyte trafficking and/or function. In this study, we characterized the functional consequences of FXIa binding to PMN leukocytes. FXIa reduced PMN leukocyte chemotaxis triggered by the chemokine, IL-8, or the bacterial-derived peptide, fMLP, perhaps as a result of the loss of directed migration. In summary, our data suggest that FXIa modulates the inflammatory response of PMN leukocytes by altering migration. These studies highlight the interplay between inflammation and coagulation and suggest that FXIa may play a role in innate immunity.

Original languageEnglish (US)
Pages (from-to)923-927
Number of pages5
JournalJournal of Leukocyte Biology
Volume90
Issue number5
DOIs
StatePublished - Nov 2011

Keywords

  • Contact system
  • Inflammation
  • Innate immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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