In vivo imaging implicates CCR2+ monocytes as regulators of neutrophil recruitment during arthritis

Baomei Wang, Bernd H. Zinselmeyer, Herbert A. Runnels, Timothy P. LaBranche, Phillip A. Morton, Daniel Kreisel, Matthias Mack, Cheryl Nickerson-Nutter, Paul M. Allen, Mark J. Miller

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The infiltration of neutrophils and monocytes is a prominent feature of inflammatory diseases including human rheumatoid arthritis. Understanding how neutrophil recruitment is regulated during pathogenesis is crucial for developing anti-inflammatory therapies. We optimized the K/B×N serum-induced mouse arthritis model to study neutrophil trafficking dynamics in vivo using two-photon microscopy. Arthritogenic serum was injected subcutaneously into one hind footpad to induce a local arthritis with robust neutrophil recruitment. Using this approach, we showed that the depletion of monocytes with clodronate liposomes impaired neutrophil recruitment specifically at the transendothelial migration step. The depletion of CCR2+ monocytes with the monoclonal antibody MC-21 reproduced these effects, implicating CCR2+ monocytes as key regulators of neutrophil extravasation during arthritis initiation. However, monocyte depletion did not prevent neutrophil extravasation in response to bacterial challenge. These findings suggest that anti-inflammatory therapies targeting monocytes may act in part through antagonizing neutrophil extravasation at sites of aseptic inflammation.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalCellular Immunology
Volume278
Issue number1-2
DOIs
StatePublished - Jul 1 2012

Keywords

  • Arthritis
  • K/B×N serum
  • Monocyte
  • Neutrophil
  • Two-photon microscopy

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