Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 200, Issue 10, Pages 1231-1241Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20032152
Keywords
chemotaxis; endothelium; inflammation; lymphatic system; macrophage
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Studying the influence of chemokine receptors (CCRs) on monocyte fate may reveal information about which subpopulations of monocytes convert to dendritic cells (DCs) and the migration pathways that they use. First, we examined whether prominent CCRs on different monocyte subsets, CCR2 or CX(3)CR1, mediated migration events upstream of the accumulation of monocyte-derived DCs in lymph nodes (LNs). Monocytes were labeled and traced by uptake of latex microspheres in skin. Unexpectedly, neither CCR2 nor CX(3)CR1 were required. However, absence of CCR2 led to an increased labeling of the minor Gr-1(int) monocyte population, and the number of latex(+) DCs that emigrated to LNs was correspondingly increased. Characterization of Gr-1(int) monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood. CCR7 and CCR8 pathways were used by monocyte-derived DCs during mobilization from skin to LNs. The role of CCR8 in emigration from tissues also applied to human monocyte-derived cells in a model of transendothelial trafficking. Collectively, the data suggest that Gr-1(int) monocytes may be most disposed to become a lymphatic-migrating DCs. When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs.
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