Identification of known and novel genes in activated monocytes from patients with rheumatoid arthritis

Stuhlmüller, Bruno; Ungethüm, Ute; Scholze, Susann; Martinez, Lorena Rodriguez; Backhaus, Marina; Kraetsch, Hans-G.; Kinne, Raimund W.; Burmester, G.-R.

doi:10.1002/1529-0131(200004)43:4<775::aid-anr8>3.0.co;2-7

Cited by 98 publications

(77 citation statements)

References 76 publications

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“…The contribution of macrophages has also been investigated in RA patients demonstrating that the number of synovial macrophages correlates with the degree of joint erosion [24,25]. Moreover, the cytokine genes for TNFa, IL-1b and IL-6 are upregulated in peripheral blood monocytes of RA patients, which may contribute to the systemic features of RA [26]. This is well in agreement with our finding of increased expression of TNFa mRNA in peritoneal macrophages from arthritic mice compared with normal mice.…”

Section: Discussionsupporting

confidence: 89%

FcγRIII‐Expressing Macrophages are Essential for Development of Collagen‐Induced Arthritis

Andrén¹,

Zou²,

Nilsson³

et al. 2006

Scand J Immunol

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IgG-binding Fc receptors, and in particular FcgRIII, are crucial for induction of collagen-induced arthritis (CIA), as FcgRIII-deficient mice are highly protected to arthritis. However, which of the FcgRIII-expressing cells that is responsible for induction of arthritis is not known. In this study, we have addressed this question by purifying different FcgRIII þ cell populations, transferred them to FcgRIII-deficient mice and studied if the recipient mice can develop arthritis. The cell populations were isolated from spleen, bone marrow and the peritoneal cavity. Our results show that FcgRIII þ CD11b þ peritoneal macrophages can render FcgRIII-deficient mice susceptible to CIA. In contrast, FcgRIII -peritoneal macrophages or FcgRIII þ spleenocytes, bone marrow cells, mast cells or monocytes could not mediate this effect. To further evaluate the contribution of the FcgRIII þ macrophages in arthritis, we investigated the cytokine profile in these cells during CIA. The arthritic macrophages exhibited significantly higher mRNA levels of TNFa and IL-12p35 compared with macrophages from normal mice. We conclude that FcgRIII-expressing macrophages, producing proinflammatory cytokine and T helper type 1 differentiating factor, are the major effector cells in the induction of CIA.

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Section: Discussionsupporting

confidence: 89%

FcγRIII‐Expressing Macrophages are Essential for Development of Collagen‐Induced Arthritis

Andrén¹,

Zou²,

Nilsson³

et al. 2006

Scand J Immunol

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“…This question is important because macrophage numbers/activation in inflamed tissues and monocyte numbers/activation in the circulation have been demonstrated to correlate with the severity of RA and other chronic inflammatory conditions (26)(27)(28)(29)(30). We showed herein that in CIA, there is an increase in the number of circulating leukocytes around the clinical onset of disease in mice that developed Figure 6.…”

Section: Discussionmentioning

confidence: 65%

“…to increase their numbers by enhancing their survival, as well as to prime/activate them, for example, to produce downstream mediators (4,(23)(24)(25). In this context, monocyte/macrophage numbers have been demonstrated to correlate with RA severity (26)(27)(28)(29)(30). It is also possible, however, that during inflammatory reactions, GM-CSF may have systemic effects, particularly as its administration can mobilize hemopoietic cells from the bone marrow and promote myelopoiesis (26).…”

mentioning

confidence: 99%

Regulation of systemic and local myeloid cell subpopulations by bone marrow cell–derived granulocyte–macrophage colony‐stimulating factor in experimental inflammatory arthritis

Cook

Turner

Braine

et al. 2011

Arthritis & Rheumatism

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Objective. Even though there are clinical trials assessing granulocyte-macrophage colony-stimulating factor (GM-CSF) blockade in rheumatoid arthritis (RA), questions remain as to how GM-CSF acts as a proinflammatory cytokine. The aims of this study on the regulation of arthritis progression by GM-CSF were to determine the source of the GM-CSF, whether there are systemic effects, the changes in synovial tissue leukocyte populations, and the arthritis model dependence on GM-CSF.Methods. Bone marrow chimeras were used to determine the source of GM-CSF required for the development of collagen-induced arthritis (CIA). The K/BxN serum-transfer model of arthritis was tested in GM-CSF ؊/؊ mice and using anti-GM-CSF monoclonal antibodies. Cell populations from arthritic mice were assessed by differential staining and flow cytometry.Results. In the CIA model, GM-CSF produced by bone marrow-derived cells was required for arthritis development. GM-CSF blockade, while ameliorating the development of CIA, was found to have systemic effects, limiting the increase in circulating Ly-6C high monocytes and neutrophils. GM-CSF blockade led to fewer synovial macrophages (both Ly-6C high and Ly-6C low ), neutrophils, and lymphocytes. In the absence of GM-CSF, K/BxN serum-transfer arthritis initially developed normally; however, the numbers of Ly-6C high monocytes and synovial macrophages (both Ly-6C high and Ly-6C low ) were again reduced, along with the peak disease severity and maintenance.Conclusion. GM-CSF is a key player in two arthritis models, participating in interactions between hemopoietic cells, both locally and systemically, to control myeloid cell numbers as well as presumably to "activate" them. These results could be useful for the analysis of current clinical trials targeting GM-CSF in patients with RA.Granulocyte-macrophage colony-stimulating factor (GM-CSF) was initially discovered by its role in the differentiation of hemopoietic precursor cells into mature granulocytes and macrophages (1); however, it can also affect mature cell function and may be considered a proinflammatory cytokine (2-4). In this context, clinical trials are in progress testing this concept in rheumatoid arthritis (RA) (4).GM-CSF is produced in vitro by a number of different cell types following exposure to various stimuli (4-8). A so-called CSF network has been proposed in which GM-CSF and other CSFs form part of a cytokinemediated hemopoietic cell-tissue cell interaction that drives chronic inflammatory reactions, for example, in joints (9). In support of this concept, several models of disease, including arthritis (10-12), multiple sclerosis Professor Hamilton has received consulting fees from MorphoSys AG and CSL, Ltd. (less than $10,000 a year). The University of Melbourne has licensed to MorphoSys AG, Germany, patented technology relating to therapeutically targeting granulocyte-macrophage colony-stimulating factor, for which licensing fees and milestone payments have been made.

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“…Similar studies of RA have yielded evidence of monocyte activation (27,28) as well as other changes (29). It is currently unclear to what extent, if any, PTPN22 signaling pathways are reflected in these findings.…”

Section: Peter K Gregersen and Franak Batliwallamentioning

confidence: 62%

PTPN22 and rheumatoid arthritis: Gratifying replication

Gregersen¹,

Batliwalla²

2005

Arthritis & Rheumatism

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Identification of known and novel genes in activated monocytes from patients with rheumatoid arthritis

Cited by 98 publications

References 76 publications

FcγRIII‐Expressing Macrophages are Essential for Development of Collagen‐Induced Arthritis

FcγRIII‐Expressing Macrophages are Essential for Development of Collagen‐Induced Arthritis

Regulation of systemic and local myeloid cell subpopulations by bone marrow cell–derived granulocyte–macrophage colony‐stimulating factor in experimental inflammatory arthritis

PTPN22 and rheumatoid arthritis: Gratifying replication

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