TY - JOUR
T1 - Differentiation to the CCR2+ inflammatory phenotype in vivo is a constitutive, time- limited property of blood monocytes and is independent of local inflammatory mediators
AU - Xu, Heping
AU - Manivannan, Ayyakkannu
AU - Dawson, Rosemary Anne
AU - Crane, Isabel Joan
AU - Mack, M.
AU - Sharp, Peter Frederick
AU - Liversidge, Janet Mary
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
KW - PLASMACYTOID DENDRITIC CELLS
KW - CENTRAL-NERVOUS-SYSTEM
KW - LYMPH-NODES
KW - MONONUCLEAR PHAGOCYTES
KW - RESIDENT MICROGLIA
KW - MOUSE
KW - MIGRATION
KW - RECRUITMENT
KW - ACTIVATION
UR - http://www.scopus.com/inward/record.url?scp=27744461686&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.175.10.6915
DO - 10.4049/jimmunol.175.10.6915
M3 - Article
C2 - 16272351
SN - 0022-1767
VL - 175
SP - 6915
EP - 6923
JO - The Journal of Immunology
JF - The Journal of Immunology
IS - 10
ER -