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CCR2‐dependent mechanisms are required for monocyte/macrophage recruitment from the bone marrow during MCMV infection
Author(s) -
Crane Meredith J,
HokenessAntonellli Kirsten L,
SalazarMather Thais P
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.452
Subject(s) - ccr2 , bone marrow , chemokine , monocyte , ccl2 , immunology , ccl7 , chemokine receptor , macrophage , biology , inflammation , in vitro , biochemistry
Murine cytomegalovirus (MCMV) is a hepatotropic β‐herpes virus. Primary infection induces a strong innate immune response with an essential role for chemokine signaling. CC chemokine receptor 2 (CCR2)‐deficient mice recruit fewer macrophages to the liver and are more susceptible to infection. This suggests a macrophage trafficking defect in the absence of CCR2 at the level of bone marrow egress or peripheral organ entry from the circulation. Studies here identify a role for CCR2 in monocyte egress from the bone marrow during MCMV infection. In contrast to wild type mice, our results demonstrate the accumulation of F4/80 + CD11b + monocyte/macrophages in the bone marrow of infected CCR2‐deficient mice. Release is likely mediated by interactions between CCR2 and one or more of its ligands, CCL2, CCL7 and CCL12. Our studies identify F4/80 + CD11b + monocyte/macrophages as major producers of these chemokines in the bone marrow during MCMV infection. In vivo trafficking studies indicate that CCR2 expression is not required for entry into peripheral organs or recirculation to the bone marrow. These results demonstrate that CCR2‐dependent mechanisms are critical in regulating the movement of monocyte/macrophages from the bone marrow but not for entry into the peripheral tissues during MCMV infection. Supported by NIH R01CA‐102708 and the Brown University Nicole Rosenthal Hartnett ‘91 Graduate Fellowship .