title: In vivo imaging implicates CCR2(+) monocytes as regulators of neutrophil recruitment during arthritis.
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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Baomei
authors.initials: B
authors.lastname: Wang
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Zinselmeyer
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Runnels
authors.forename: Timothy P
authors.initials: TP
authors.lastname: LaBranche
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Morton
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Cheryl
authors.initials: C
authors.lastname: Nickerson-Nutter
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D004002:Clodronic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D054390:Receptors, CCR2 / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; C515335:Ccr2 protein, mouse; D008081:Liposomes; D054390:Receptors, CCR2; D004002:Clodronic Acid