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


RESULTS
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.


CONCLUSIONS
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.
Gladstone Institute of Cardiovascular Disease, San Francisco, California, United States of America.
Noah
N
Saederup
Astrid E
AE
Cardona
Kelsey
K
Croft
Makiko
M
Mizutani
Anne C
AC
Cotleur
Chia-Lin
CL
Tsou
Richard M
RM
Ransohoff
Israel F
IF
Charo
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D000097573:Red Fluorescent Protein
D008164:Luminescent Proteins; D054390:Receptors, CCR2; D000097573:Red Fluorescent Protein