Monocyte Subsets (monocyte + subset)

Distribution by Scientific Domains


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 nave 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]


Fc, receptor,dependent expansion of a hyperactive monocyte subset in lupus-prone mice

ARTHRITIS & RHEUMATISM, Issue 8 2009
Marie-Laure Santiago-Raber
Objective Lupus-prone BXSB mice develop monocytosis characterized by selective accumulation of the Gr-1, monocyte subset. The aim of this study was to explore the possible role of activating IgG Fc receptors (Fc,R) in the development of monocytosis and to characterize the functional phenotype of the Gr-1, subset that accumulates in lupus-prone mice bearing the NZB-type defective Fcgr2b allele for the inhibitory Fc,RIIB. Methods The development of monocytosis was analyzed in BXSB and anti-IgG2a rheumatoid factor,transgenic C57BL/6 mice deficient in activating Fc,R. Moreover, we assessed the expression levels of activating Fc,R and inhibitory Fc,RIIB on Gr-1+ and Gr-1, monocyte subsets in C57BL/6 mice bearing the C57BL/6-type or the NZB-type Fcgr2b allele. Results We observed monocytosis with expansion of the Gr-1, subset in anti-IgG2a,transgenic C57BL/6 mice expressing IgG2a, but not in those lacking IgG2a. Moreover, monocytosis barely developed in BXSB and anti-IgG2a,transgenic C57BL/6 mice deficient in activating Fc,R. The Gr-1, subset that accumulated in lupus-prone mice displayed a unique hyperactive phenotype. It expressed very low levels of inhibitory Fc,RIIB, due to the presence of the NZB-type Fcgr2b allele, but high levels of activating Fc,RIV. This was in contrast to high levels of Fc,RIIB expression and no Fc,RIV expression on the Gr-1+ subset. Conclusion Our results demonstrated a critical role of activating Fc,R in the development of monocytosis and in the expansion of a Gr-1,Fc,RIIBlowFc,RIV+ hyperactive monocyte subset in lupus-prone mice. Our findings further highlight the importance of the NZB-type Fcgr2b susceptibility allele in murine lupus, the presence of which induces increased production of hyperactive monocytes as well as dysregulated activation of autoreactive B cells. [source]


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 nave 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]


HLA-DR expression and differential trafficking of monocyte subsets following low to intermediate risk surgery,

ANAESTHESIA, Issue 1 2010
J. M. Handy
Summary Reduced HLA-DR expression on monocytes has been suggested as a predictive marker of immunosuppression following very high risk surgery, but there are few reports in lower risk surgery. In 32 patients undergoing low to intermediate risk surgery, blood samples were analysed by flow cytometry for HLA-DR expression and numbers in both CD14high and CD14lowCD16+ monocyte subsets. The numbers of CD14high monocytes increased at 24 h (mean (SD), 5.0 (2.2) vs 7.6 (3.9) 105 cells.ml,1; p < 0.01) while CD14lowCD16+ monocytes decreased (0.68 (0.36) vs 0.44 (0.36) 105 cells.ml,1; p < 0.01). HLA-DR expression was significantly reduced in both subsets by 24 h (mean (SD) fluorescent intensity 440 (310) vs 160 (130) for CD14high and 1000 (410) vs 560 (380) for CD14lowCD16+ subsets; p < 0.01). This reduction of monocyte HLA-DR expression 24 h following lower risk surgery raises questions about the purported clinical utility of this biomarker as an early predictor of postoperative complications. Our results also suggest that surgery induces significant trafficking (i.e. mobilisation, margination and extravasation) of monocyte subsets, and that monocyte HLA-DR depression is the result of a down-regulatory phenomenon (decreased protein expression on each cell) rather than the differential trafficking of monocyte subsets. [source]


Fc, receptor,dependent expansion of a hyperactive monocyte subset in lupus-prone mice

ARTHRITIS & RHEUMATISM, Issue 8 2009
Marie-Laure Santiago-Raber
Objective Lupus-prone BXSB mice develop monocytosis characterized by selective accumulation of the Gr-1, monocyte subset. The aim of this study was to explore the possible role of activating IgG Fc receptors (Fc,R) in the development of monocytosis and to characterize the functional phenotype of the Gr-1, subset that accumulates in lupus-prone mice bearing the NZB-type defective Fcgr2b allele for the inhibitory Fc,RIIB. Methods The development of monocytosis was analyzed in BXSB and anti-IgG2a rheumatoid factor,transgenic C57BL/6 mice deficient in activating Fc,R. Moreover, we assessed the expression levels of activating Fc,R and inhibitory Fc,RIIB on Gr-1+ and Gr-1, monocyte subsets in C57BL/6 mice bearing the C57BL/6-type or the NZB-type Fcgr2b allele. Results We observed monocytosis with expansion of the Gr-1, subset in anti-IgG2a,transgenic C57BL/6 mice expressing IgG2a, but not in those lacking IgG2a. Moreover, monocytosis barely developed in BXSB and anti-IgG2a,transgenic C57BL/6 mice deficient in activating Fc,R. The Gr-1, subset that accumulated in lupus-prone mice displayed a unique hyperactive phenotype. It expressed very low levels of inhibitory Fc,RIIB, due to the presence of the NZB-type Fcgr2b allele, but high levels of activating Fc,RIV. This was in contrast to high levels of Fc,RIIB expression and no Fc,RIV expression on the Gr-1+ subset. Conclusion Our results demonstrated a critical role of activating Fc,R in the development of monocytosis and in the expansion of a Gr-1,Fc,RIIBlowFc,RIV+ hyperactive monocyte subset in lupus-prone mice. Our findings further highlight the importance of the NZB-type Fcgr2b susceptibility allele in murine lupus, the presence of which induces increased production of hyperactive monocytes as well as dysregulated activation of autoreactive B cells. [source]