Differentiation to the CCR2+ inflammatory phenotype in vivo is a constitutive, time- limited property of blood monocytes and is independent of local inflammatory mediators

Heping Xu, Ayyakkannu Manivannan, Rosemary Anne Dawson, Isabel Joan Crane, M. Mack, Peter Frederick Sharp, Janet Mary Liversidge

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

It is proposed that CCR2(+) monocytes are specifically recruited to inflammatory sites, whereas CCR2(-) monocytes are recruited to normal tissue to become resident macrophages. Whether these subsets represent separate lineages, how differential trafficking is regulated and whether monocytes undergo further differentiation is uncertain. Using a mouse model of autoimmune uveoretinitis we examined monocyte trafficking to the inflamed retina in vivo. We show that bone marrow-derived CD11b(+) F4/80(-) monocytes require 24 to 48 h within the circulation and lymphoid system before acquiring the CCR2(+) phenotype and trafficking to the inflamed retina is enabled. This phenotype, and the capacity to traffic were lost by 72 h. Monocyte CCR2 expression followed a similar time course in normal mice indicating that differentiation to an inflammatory phenotype is a constitutive, time-limited property, independent of local inflammatory mediators. Phenotypic analysis of adoptively transferred cells indicated that circulating inflammatory monocytes also differentiate into CD11c(+) and B220(+) dendritic cells and F4/80(+) tissue macrophages in vivo. Our data supports the hypothesis of continuous extravasation and progressive differentiation over time of inflammatory monocytes in the circulation rather than replication within the actively inflamed tissue, and supports the concept of myeloid dendritic cell differentiation from trafficking monocytes under physiological conditions in vivo.

Original languageEnglish
Pages (from-to)6915-6923
Number of pages8
JournalThe Journal of Immunology
Volume175
Issue number10
DOIs
Publication statusPublished - Nov 2005

Keywords

  • EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
  • PLASMACYTOID DENDRITIC CELLS
  • CENTRAL-NERVOUS-SYSTEM
  • LYMPH-NODES
  • MONONUCLEAR PHAGOCYTES
  • RESIDENT MICROGLIA
  • MOUSE
  • MIGRATION
  • RECRUITMENT
  • ACTIVATION

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