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

Wang, Baomei and Zinselmeyer, Bernd H. and Runnels, Herbert A. and LaBranche, Timothy P. and Morton, Phillip A. and Kreisel, Daniel and Mack, Matthias and Nickerson-Nutter, Cheryl and Allen, Paul M. and Miller, Mark J. (2012) In vivo imaging implicates CCR2(+) monocytes as regulators of neutrophil recruitment during arthritis. CELLULAR IMMUNOLOGY, 278 (1-2). pp. 103-112. ISSN 0008-8749,

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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 x 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. (C) 2012 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: COLLAGEN-INDUCED ARTHRITIS; AUTOANTIBODY-MEDIATED ARTHRITIS; FIBROBLAST-LIKE SYNOVIOCYTES; CXC-CHEMOKINE RECEPTORS; RHEUMATOID-ARTHRITIS; CC-CHEMOKINE; INFLAMMATORY MONOCYTES; LEUKOCYTE RECRUITMENT; AUTOIMMUNE-DISEASE; MURINE MODEL; Arthritis; Neutrophil; Monocyte; Two-photon microscopy; K/B x N serum
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 11 May 2020 05:45
Last Modified: 11 May 2020 05:45
URI: https://pred.uni-regensburg.de/id/eprint/18464

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