Expression of Selectin Families and Their Ligand Sialyl Lewis X in the Muscles of Inflammatory Myopathies. An Immunohistochemical Study.

Jimi, Takahiro; Wakayama, Yoshihiro; Murahashi, Makoto; Inoue, Masahiko; Shibuya, Seiji; Yamashita, Sumimasa; Misugi, N; Kobayashi, Takuya

doi:10.2169/internalmedicine.38.632

Cited by 9 publications

(9 citation statements)

References 18 publications

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“…The endothelial expressions of MECA-79 epitopes, sulfated extended core 1 lactosamine structures , 28 have been shown earlier to be induced during inflammation at the sites of acute transplant rejection, bronchial asthma, as well as inflamed muscle or skin lesions. 3,29,30 Here we expand these observations and show that endothelial mAb MECA-79 reactivity was present in many sites of inflammations, such as thyroiditis, psoriasis, ulcerative colitis, asthma, and organ transplant rejections.…”

Section: Discussionsupporting

confidence: 61%

Glycosylation Might Provide Endothelial Zip Codes for Organ-Specific Leukocyte Traffic into Inflammatory Sites

Renkonen

Tynninen

Häyry

et al. 2002

The American Journal of Pathology

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Inflammatory diseases, such as acute kidney and heart allograft rejections or bronchial asthma, are characterized by a heavy infiltration of lymphocytes and monocytes, but not of granulocytes, leading finally to necrotic changes at the inflammatory site. [1][2][3][4] The recruitment of lymphocytes across the microvascular postcapillary endothelium 5-7 is a complex cascade, taking its origin from the initial tethering and rolling of leukocytes that are mediated by the members of the selectin family and their glycosylated ligands. These interactions are followed by a chemokine-mediated activation of integrins, leading to a firm adhesion of rolling leukocytes and, subsequently, to transendothelial migration into inflammatory sites. 8,9 The tethering and rolling phases of lymphocyte extravasation have been proposed to be initiated by L-selectin. This molecule recognizes endothelial ligands, such as CD34, podocalyxin, MAdCAM-1, and sgp200, provided that these ligands are decorated with ␣2,3-sialylated, ␣1,3-fucosylated, and sulfated lactosamines. 1,5-7,10 -12 These sulfated sialyl Lewis x (sLex) glycans are necessary for the L-selectin-mediated binding of lymphocytes to endothelium and are constantly expressed at least on the CD34 glycans of lymph node high endothelium. 13 Under normal conditions, the flat endothelium in parenchymal organs does not express properly glycosylated modifications of L-selectin ligands 14 and no extravasation occurs. However, the induction of sLex-or sulfo sLex-decorated L-selectin ligands onto the postcapillary microvascular endothelium occurs both in rodents and humans undergoing heart and kidney allograft rejection and also in the early specimens taken from bronchial asthma patients. [2][3][4]14 Moreover, the enzymatically synthesized multivalent sLex glycans can prevent the selectin-dependent lymphocyte adhesion to properly glycosylated endothelium ex vivo, pointing out a putative mean to inhibit the inflammatory reaction. 14,15 Here we expand these previous observations and analyze the endothelial sLex or sulfo sLex expression patterns in various inflammatory diseases. For this purpose, a large series of histological biopsies (Ͼ400) from patients with ulcerative colitis, psoriasis, thyroiditis, myocarditis, and vasculitis and their corresponding noninflamed tissues were collected. The endothelium of control noninflamed tissues did not express essentially any sLex or sulfo sLex epitopes whereas on the endothelium of inflamed organs they were prominently expressed. Most importantly, the up-regulated sLex or sulfo sLex expression patterns of inflamed tissues were clearly different between every organ analyzed, and when combined with

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Section: Discussionsupporting

confidence: 61%

Glycosylation Might Provide Endothelial Zip Codes for Organ-Specific Leukocyte Traffic into Inflammatory Sites

Renkonen

Tynninen

Häyry

et al. 2002

The American Journal of Pathology

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“…In addition to the recent theory described above, several mechanisms may be proposed and associated: 1) the blockade of IgG Fc receptors on phagocytic cells by the infused IVIG, thereby preventing the removal of cells, sensitized with autoantibodies of IgG isotype, from the circulation; 2) the presence of antiidiopathic antibodies capable of suppressing autoantibody secretion in the pool of plasma donors used for IVIG production; 3) a direct effect on B and T lymphocytes; 4) the inhibition of adhesion molecules and cytokine production; and/or 5) the presence of soluble CD4, CD8, and HLA in IVIG, which modify antigen recognition by target cells. These 2 last theories are probably important, since IVIG might also provide a source of antiidiotypic antibodies directed against chemokines, HLA antigens, adhesion molecules, and especially the selectin family, and antiapoptotic molecules and metalloproteases, which are known to be involved in the pathogenesis of myositis (22,(33)(34)(35)(36)(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Results and long‐term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: An open study with thirty‐five adult patients

Chérìn

Pelletier

Teixeira

et al. 2002

Arthritis & Rheumatism

225

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Objective. Polymyositis is a rare inflammatory muscular disease of unknown cause. Corticosteroids and immunosuppressive drugs are the first choice of therapy but are not always effective and may cause serious side effects. Many studies have shown that polyvalent intravenous immunoglobulin (IVIG) may be of interest for the treatment of dermatomyositis. We carried out an open, prospective study to evaluate the efficacy of IVIG in subjects with polymyositis that was refractory to traditional treatments, and we evaluated the benefits of this therapy over a long-term period of followup.Methods. Thirty-five adult white patients (20 female, 15 male, mean age 43.5 years [SD 16.8]) with chronic, refractory polymyositis were treated with high doses of IVIG, after the patients had received the following traditional treatments: prednisone (n ‫؍‬ 35), methotrexate (n ‫؍‬ 24), azathioprine (n ‫؍‬ 13), cyclophosphamide (n ‫؍‬ 4), cyclosporine (n ‫؍‬ 7), chlorambucil (n ‫؍‬ 1), plasmapheresis (n ‫؍‬ 8), lymphopheresis (n ‫؍‬ 1), and total body irradiation (n ‫؍‬ 1). There had been no changes in the patients' treatment in the 2 months before the initiation of IVIG therapy, and doses were not increased during IVIG treatment. We used preparations of polyvalent human IVIG with increased concentrations of intact IgG. The patients received 1 gm/kg/day for 2 consecutive days per month. The mean course of treatment was 4-6 months. The clinical assessment involved the evaluation of proximal muscle power, muscle disability scale score, and esophageal disorders. The biochemical evaluations carried out before each treatment period were compared by Student's t-test and nonparametric Wilcoxon test. Results were considered to be significant at P ‫؍‬ 0.05.Results. In the short-term, significant clinical improvement was noted in 25 of the 35 patients (71.4%). Mean muscle power was estimated before and after IVIG therapy and was found to be significantly improved (P < 0.01). All patients had a significant biochemical response. Mean creatine kinase levels during IVIG therapy decreased significantly before the fourth IVIG perfusion (P < 0.01). Side effects, usually minor, were noted in 6 patients. This benefit allowed the initial prednisone dose to be reduced by >50% in all patients. The mean (؎SD) followup time for the 25 patients who responded favorably to IVIG treatment was 51.4 ؎ 13.1 months. Twelve of these 25 patients remained in full remission following their initial course of IVIG, resulting in complete stoppage of medication in 5 patients or low doses of steroids in 7 patients. The condition of 6 patients remained improved and no other drugs were prescribed, but the patients remained dependent on IVIG infusions. Seven of the 25 patients who responded well to IVIG treatment relapsed at an average of 17.1 months (range 4-23 months) after the discontinuation of IVIG. Conclusion. IVIG is an interesting therapy for the treatment of polymyositis, with results showing that the

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“…Expression of E-selectin in all endothelial cells in PM and DM was recorded by some authors 73 whereas others 28 observed it only in arterioles and venules. E-selectin expression was not recorded in most studies.…”

Section: Functional Roles Of Cytokines Cell Adhesion Molecules and mentioning

confidence: 92%

“…28,39,92 P-selectin expression was observed in endothelial cells, expression being stronger in PM than in DM, and in venules than in arterioles. 73 In keeping, SLe x , a common ligand for these selectins, was recorded in infiltrating leukocytes, interstitial tissues, and endothelial cells but also in some muscle fibers.…”

Section: Functional Roles Of Cytokines Cell Adhesion Molecules and mentioning

confidence: 94%

Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies

et al. 2003

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The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector response appears to be humoral and directed against the microvasculature, whereas in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade and eventually destroy nonnecrotic muscle fibers expressing major histocompatibility complex class I. The need for more specific and safer therapies in inflammatory myopathies has prompted researchers to better decipher the molecular events associated with inflammation and muscle fiber loss in these diseases. The complex specific migration of leukocyte subsets to target tissues requires a coordinated series of events, namely activation of leukocytes, adhesion to the vascular endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a major role in this multistep process. In addition, cytokines by stimulating CAM expression and orchestrating T-cell differentiation also influence the immune response. This review focuses on recent advances in defining the molecular events involved in leukocyte trafficking in inflammatory myopathies. Specific topics include a concise summary of clinical features, pathological findings and immunopathology observed in inflammatory myopathies, background information about cytokines, chemokines and cell adhesion molecules, and the expression of these molecules in inflammatory myopathies.

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Expression of Selectin Families and Their Ligand Sialyl Lewis X in the Muscles of Inflammatory Myopathies. An Immunohistochemical Study.

Cited by 9 publications

References 18 publications

Glycosylation Might Provide Endothelial Zip Codes for Organ-Specific Leukocyte Traffic into Inflammatory Sites

Glycosylation Might Provide Endothelial Zip Codes for Organ-Specific Leukocyte Traffic into Inflammatory Sites

Results and long‐term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: An open study with thirty‐five adult patients

Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies

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