Polymorphonuclear granulocytes at the pannus‐cartilage junction in rheumatoid arthritis

Mohr, W.; Menninger, H.

doi:10.1002/art.1780231224

Cited by 43 publications

(22 citation statements)

References 2 publications

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“…The predominant cell types at the cartilage-pannus junction in established RA are macrophages and synovial fibroblasts (42). However, neutrophils can also be found at this site, as well as in the joint exudate (39,43,44). These findings suggest that SOCS-3 and SOCS-1 have nonredundant functions in regulating myeloid lineage cells and that SOCS-1 may be more important for macrophage responses, whereas SOCS-3 plays a critical role in regulation of neutrophil responses during inflammation.…”

Section: Figurementioning

confidence: 87%

SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis

Wong

Egan²,

Croker³

et al. 2006

Journal of Clinical Investigation

186

141

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RA is an autoimmune disease characterized by sustained imbalance between pro-and antiinflammatory immune mechanisms. The SOCS proteins are negative regulators of cytokine signaling, but to date there has been little information on their function in disease. The generation of Socs3 -/Dvav mice, which lack SOCS-3 in the hematopoietic and endothelial cell compartment, allowed us to explore the role of endogenous SOCS-3 during acute inflammatory arthritis. Joint inflammation in Socs3 -/Dvav mice was particularly severe and was characterized by increased numbers of neutrophils in the inflamed synovium, bone marrow, peripheral blood, and spleen. These features were most likely due to increased production of and enhanced responsiveness to G-CSF and IL-6 during arthritis in these mice. Local osteoclast generation and bone destruction were also dramatically increased in the absence of SOCS-3, as was macrophage activation. Finally, SOCS-3 was found to negatively regulate CD4 + T lymphocyte activation, including production of the pleiotropic cytokine IL-17. The absence of SOCS-3 therefore had dramatic effects in this disease model, with a broader impact on cellular responses than SOCS-1 deficiency. These findings provide direct in vivo evidence that endogenous SOCS-3 is a critical negative regulator of multiple cell types orchestrating inflammatory joint disease.

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Section: Figurementioning

confidence: 87%

SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis

Wong

Egan²,

Croker³

et al. 2006

Journal of Clinical Investigation

186

141

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“…Tissue destruction and bone erosion in RA is mediated, at least in part, by proteolytic enzymes and free radicals released by infiltrating neutrophils into the joints during repeated acute episodes (1)(2)(3)26). The role of IL-23 and IL-17 in the recruitment of neutrophils leading to the pathogenesis of RA is supported by substantial experimental and clinical evidence (5,14).…”

Section: Discussionmentioning

confidence: 99%

“…The recruited neutrophils contribute to the development of hyperplasia of the synovial tissue, pannus formation, and subsequent cartilage and bone destruction (1)(2)(3).…”

mentioning

confidence: 99%

Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNγ production

Lemos

Grespan

Vieira

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

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IL-23/IL-17-induced neutrophil recruitment plays a pivotal role in rheumatoid arthritis (RA). However, the mechanism of the neutrophil recruitment is obscure. Here we report that prostaglandin enhances the IL-23/IL-17-induced neutrophil migration in a murine model of RA by inhibiting IL-12 and IFN γ production. Methylated BSA (mBSA) and IL-23-induced neutrophil migration was inhibited by anti-IL-23 and anti-IL-17 antibodies, COX inhibitors, IL-12, or IFNγ but was enhanced by prostaglandin E 2 (PGE 2 ). IL-23-induced IL-17 production was increased by PGE 2 and suppressed by COX-inhibition or IL-12. Furthermore, COX inhibition failed to reduce IL-23-induced neutrophil migration in IL-12- or IFNγ-deficient mice. IL-17-induced neutrophil migration was not affected by COX inhibitors, IL-12, or IFNγ but was inhibited by MK886 (a leukotriene synthesis inhibitor), anti-TNFα, anti-CXCL1, and anti-CXCL5 antibodies and by repertaxin (a CXCR1/2 antagonist). These treatments all inhibited mBSA- or IL-23-induced neutrophil migration. IL-17 induced neutrophil chemotaxis through a CXC chemokines-dependent pathway. Our results suggest that prostaglandin plays an important role in IL-23-induced neutrophil migration in arthritis by enhancing IL-17 synthesis and by inhibiting IL-12 and IFNγ production. We thus provide a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also suggest an additional mechanism of action for nonsteroidal anti-inflammatory drugs.

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“…Leukocyte infiltration is an important pathological feature of many inflammatory diseases (Ajuebor et al, 2002;Edwards and Hallett, 1997;Goulding et al, 1998;Kasama et al, 2005), they are recovered from bronchoalveolar lavage fluid in asthmatic patients, indicating that they move through the endothelium and extracellular matrix and migrate across epithelium into airways (Liu et al, 1999), and are also found in arthritic joints at the pannus-cartilage junction, the site of joint-destroying erosions (Mohr and Menninger, 1980); neutrophils within the joint are now recognized to participate directly in chronic inflammation . Stress can affect inflammatory diseases (see Black, 2002(Black, 2002a for review), in part mediated by the effect of stress hormones on leukocyte function (Bierhaus et al, 2006;Bilbo et al, 2002;Dhabhar, 2002;Landmann et al, 1984;O'Leary et al, 1996;Shephard, 2003), and catecholamines mediate interactions between the sympathetic and the immune systems, to alter immune cell activity (Benschop et al, 1997;Downing and Miyan, 2000;Elenkov et al, 2000;Oberbeck, 2006;Straub et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

β2-Adrenergic receptor-dependent sexual dimorphism for murine leukocyte migration

Coupade¹,

Brown²,

Dazin

et al. 2007

Journal of Neuroimmunology

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In wild-type FVB mice, leukocyte recruitment to lipopolysaccharide was sexually dimorphic, with a greater number of leukocytes recruited in females. In male β 2 -adrenergic receptor knock out mice (bred on a congenic FVB background) the number leukocytes recruited was increased ~4-fold, while in females there was no change, eliminating sexual dimorphism in leukocyte migration. While there were significantly fewer recruited CD62L + and CD11a + leukocytes in wild-type males, only in male β 2 -adrenergic receptor knock out mice was there an increase in the number of recruited CD11a + leukocytes, again eliminating sexual dimorphism. Thus, leukocyte migration and CD11a + adhesion molecule expression in male, but not in female, leukocytes is β 2 -adrenergic receptor-dependent. Our findings provide support for a role of β 2 -adrenergic receptor mechanisms in the inflammatory response, and suggest that β 2 -adrenergic receptor on male leukocytes contributes to sexual dimorphism in the effect of stress on inflammatory diseases.

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Polymorphonuclear granulocytes at the pannus‐cartilage junction in rheumatoid arthritis

Abstract: A BFigure 1, A and B. Polymorphonuclear granulocytes (arrows) accumulating at the pannuscartilage junction (K=cartilage). (Naphthol-AS-D-chloroacetate staining; nuclear staining with hematoxylin. Magnification X 328.)

Cited by 43 publications

References 2 publications

SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis

SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis

Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNγ production

β2-Adrenergic receptor-dependent sexual dimorphism for murine leukocyte migration

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