Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice

PLoS One. 2010 Oct 27;5(10):e13693. doi: 10.1371/journal.pone.0013693.

Abstract

Background: Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.

Methodology/principal findings: We created CCR2-red fluorescent protein (RFP) knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi)/CCR2(hi) monocytes. Surprisingly, neutrophils, not Ly6C(lo) monocytes, largely replaced Ly6C(hi) cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.

Conclusion/significance: These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / cytology
  • Central Nervous System / metabolism*
  • Luminescent Proteins / genetics
  • Mice
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism*

Substances

  • Luminescent Proteins
  • Receptors, CCR2
  • red fluorescent protein