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Marrow Monocytes (marrow + monocyte)

Distribution by Scientific Domains
Medical Sciences75%

Kinds of Marrow Monocytes

  • bone marrow monocyte
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    Selected Abstracts

    Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis,

    HEPATOLOGY, Issue 1 2009
    Karlin Raja Karlmark
    In addition to liver-resident Kupffer cells, infiltrating immune cells have recently been linked to the development of liver fibrosis. Blood monocytes are circulating precursors of tissue macrophages and can be divided into two functionally distinct subpopulations in mice: Gr1hi (Ly6Chi) and Gr1lo (Ly6Clo) monocytes. The role of these monocyte subsets in hepatic fibrosis and the mechanisms of their differential recruitment into the injured liver are unknown. We therefore characterized subpopulations of infiltrating monocytes in acute and chronic carbon tetrachloride (CCl4)-induced liver injury in mice using flow cytometry and immunohistochemistry. Inflammatory Gr1hi but not Gr1lo monocytes are massively recruited into the liver upon toxic injury constituting an up to 10-fold increase in CD11b+F4/80+ intrahepatic macrophages. Comparing wild-type with C-C chemokine receptor (CCR2)-deficient and CCR2/CCR6,deficient mice revealed that CCR2 critically controls intrahepatic Gr1hi monocyte accumulation by mediating their egress from bone marrow. During chronic liver damage, intrahepatic CD11b+F4/80+Gr1+ monocyte-derived cells differentiate preferentially into inducible nitric oxide synthase,producing macrophages exerting proinflammatory and profibrogenic actions, such as promoting hepatic stellate cell (HSC) activation, T helper 1,T cell differentiation and transforming growth factor , (TGF-,) release. Impaired monocyte subset recruitment in Ccr2,/, and Ccr2,/,Ccr6,/, mice results in reduced HSC activation and diminished liver fibrosis. Moreover, adoptively transferred Gr1hi monocytes traffic into the injured liver and promote fibrosis progression in wild-type and Ccr2,/,Ccr6,/, mice, which are otherwise protected from hepatic fibrosis. Intrahepatic CD11b+F4/80+Gr1+ monocyte-derived macrophages purified from CCl4 -treated animals, but not naïve bone marrow monocytes or control lymphocytes, directly activate HSCs in a TGF-,,dependent manner in vitro. Conclusion: Inflammatory Gr1+ monocytes, recruited into the injured liver via CCR2-dependent bone marrow egress, promote the progression of liver fibrosis. Thus, they may represent an interesting novel target for antifibrotic strategies. (HEPATOLOGY 2009;50:261,274.) [source]

    Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2010
    Anke J Roelofs
    Abstract Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647,labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research [source]

    The differential effects of the radioprotectant drugs amifostine and sodium selenite treatment in combination with radiation therapy on constituent bone cells, ewing's sarcoma of bone tumor cells, and rhabdomyosarcoma tumor cells in vitro

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2008
    Bryan S. Margulies
    Abstract The purpose of this study was to determine the differential effects of therapeutic X-radiation on constituent bone cells relative to the pediatric tumor cells: Ewing's sarcoma of bone and rhabdomyosarcoma. In addition, the radioprotectant drugs amifostine and sodium selenite were administered to constituent bone cells and the two tumor cells to determine if the radioprotectants differentially protect bone cells while not benefiting the tumor cells. These studies are a necessary first step in determining the potential clinical benefit of radioprotective therapy. An established in vitro cell culture model employing both constituent bone cells (osteoblasts, primary bone marrow monocytes, osteoclasts chondrocytes, and endothelial cells) and the tumor cells lines (Ewing's sarcoma of bone and rhabdomyosarcoma) were exposed to irradiation, amifostine, and sodium selenite. Cells were then assayed for changes in cell number, cytotoxicity, mineralization, bone resorption, cell attachment, osteocalcin, caspase-3 expression, clonogenic survival, and alkaline phosphatase expression. Radiation therapy differentially decreased cell number; with osteoblasts being shown to be the least sensitive to irradiation, the tumor cells had an intermediate sensitivity and monocytes were the most sensitive. Both amifostine and sodium selenite protected chondrocytes and osteoblasts from the negative effects of irradiation, while not protecting the tumor cells. The pediatric tumor cell lines were generally more radiosensitive than the bone cells examined. The radioprotectant drugs amifostine and sodium selenite provided significant radioprotection to constituent bone cells while not protecting the tumor cells. Finally, amifostine and sodium selenite therapy provided an additional benefit beyond radioprotection by increasing cytotoxicity in nonirradiated and irradiated tumor cells. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1512,1519, 2008 [source]