Inhaled Corticosteroids Increase Siglec-5/14 Expression in Sputum Cells of COPD Patients

Wielgat, Przemysław; Mróz, Robert; Stasiak-Barmuta, Anna; Szepiel, Paweł; Chyczewska, E; Braszko, Jan J.; Hołownia, Adam

doi:10.1007/5584_2014_51

Cited by 12 publications

(12 citation statements)

References 15 publications

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“…Although it has been reported that Siglec-5/14 is increased in the sputum of COPD patients as a result of inhaled CSs [16], our in vitro data indicate that monocyte Siglec-14 expression is unaffected by treatment with prednisolone. This would need to be confirmed using patient samples, however, by measuring monocyte Siglec-14 expression levels before and after glucocorticoid treatment.…”

Section: Discussioncontrasting

confidence: 73%

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Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity

et al. 2017

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Objective. Siglecs are sialic acid-binding immunoglobulin-like lectins expressed on the surface of immune cells, which participate in the discrimination of self and non-self. We investigated myeloid CD33-related Siglec expression in a cohort of patients with SLE. Methods. Cell surface expression of Siglec-5/14, Siglec-9 and Siglec-10 on peripheral myeloid subsets were analysed from 39 SLE patients using flow cytometry. Genotyping of the Siglec-5/14 locus was also performed. Clinical markers of SLE disease activity, including SLEDAI, serum complement concentrations and serum autoantibodies, were assessed and correlated with Siglec levels. Results. Siglec-14 expression on SLE monocytes (median = 518, interquartile range: 411) was significantly higher when compared with healthy controls (median = 427, interquartile range: 289.3; P < 0.05) and correlated positively with SLEDAI scoring and anti-Sm and anti-SSB autoantibodies (P < 0.05). A negative correlation was determined with patient serum C3 concentrations (P < 0.005). Genotyping of the Siglec-5/14 locus revealed a high frequency of the Siglec-14 null allele across both groups, reflecting the incidence in Asian populations. Conclusion. Our data suggest that the Siglec immunomodulatory molecules, in particular Siglec-14 expression on monocytes, may play an important role in the inflammatory events of SLE. No bias was found with regard to SIGLEC14 genotype in our patient group compared with healthy controls. Larger comparisons of mixed ethnicity might, however, reveal an important role for Siglecs in the pathogenesis of autoimmune disease.

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Section: Discussioncontrasting

confidence: 73%

“…It has been reported that inhaled CSs increase Siglec-5/14 expression in the sputum of patients with COPD [16]. Given that CSs are a mainstay of treatment for patients with SLE (Table 1), we sought to determine the effects of overnight prednisolone treatment on donor PBMC Siglec-14 expression.…”

Section: Resultsmentioning

confidence: 99%

Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity

et al. 2017

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“…In this way, Siglec-7 can potentially dampen anti-tumor immunity and promote cancer invasion [ 55 ]. Additionally, it has been demonstrated previously, that glucocorticosteroids increase expression of several Siglecs in immune cells in vivo [ 56 , 57 ]. Given the importance of sialylation and Siglecs in immunity it is reasonable to speculate that Dex can be crucial factor regulating immunogenic potential of gliomas and immunosuppressive phenotype and survival of tumor-associated immune cells.…”

Section: Discussionmentioning

confidence: 99%

Sialic acids as cellular markers of immunomodulatory action of dexamethasone on glioma cells of different immunogenicity

et al. 2018

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Glucocorticosteroids, including dexamethasone (Dex), are commonly used to control tumor-induced edema in the brain tumor patients. There are increasing evidences that immunosuppressive action of Dex interferes with immune surveillance resulting in lower patients overall survival; however, the mechanisms underlying these actions remain unclear. Changes in the expression of sialic acids are critical features of many cancers that reduce their immunogenicity and increase viability. Sialoglycans can be recognized by CD33-related Siglecs that negatively regulate the immune response and thereby impair immune surveillance. In this study, we analysed the effect of Dex on cell surface sialylation pattern and recognition of these structures by Siglec-F receptor in poorly immunogenic GL261 and immunogenic SMA560 glioma cells. Relative amount of α2.3-, α2.6- and α2.8-linked sialic acids were detected by Western blot with MAA ( Maackia amurensis) and SNA ( Sambucus nigra ) lectins, and flow cytometry using monoclonal antibody anti-PSA-NCAM. In response to Dex, α2.8 sialylation in both, GL261 and SMA560 was increased, whereas the level of α2.3-linked sialic acids remained unchanged. Moreover, we found the opposite effects of Dex on α2.6 sialylation in poorly immunogenic and immunogenic glioma cells. Furthermore, changes in sialylation pattern were accompanied by dose-dependent effects of Dex on Siglec-F binding to glioma cell membranes as well as decreased α-neuraminidase activity. These results suggest that glucocorticosteroid-induced alterations in cell surface sialylation and Siglecs recognition may dampen anti-tumor immunity, and participate in glioma-promoting process by immune cells. Our study gives new view on corticosteroid therapy in glioma patients.

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“…In humans, the siglec gene cluster has the Siglec-14 and Siglec-5 genes, while the Siglec-14 null allele contains the Siglec-5/14 fusion gene. Imbalance in Siglec-5/14 expression promotes initiation of inflammatory mechanisms in COPD [94]. The level of Siglec-14 affects the frequency of COPD exacerbations [95].…”

Section: Reviewsmentioning

confidence: 99%

Sialic Acid-Binding Lectins as Potential Pathophysiological Targets in Treatment of Chronic Bronchopulmonary Diseases (Review)

Kytikovа¹,

Gvozdenko²,

Аntonyuk³

et al. 2019

Sovrem Tehnol Med

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The article is devoted to the problem of finding the pathophysiological targets for optimizing the treatment of common and socially significant chronic respiratory diseases-bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). The balance between pro-inflammatory and anti-inflammatory mechanisms determines the nature of inflammation in these diseases. Among the regulators of inflammation there are siglecs-sialic acid-binding immunoglobulin-like lectins able to interact with terminal sialic acid present in all cells. Siglecs are involved in regulating cell proliferation, differentiation, apoptosis and implementing cell-cell interactions. The key role in modulating the regulatory activity of siglecs is in their ability to interact with ligands. Although research on the structure and biological functions of siglecs in the body has only recently started, the prospects for this research are promising, especially with respect to BA and COPD treatment. Siglecs are mainly expressed by immune and peripheral blood cells. Pathophysiological mechanisms of BA and COPD are implemented with participation of eosinophils, mast cells, neutrophils, and macrophages. The siglecs expressed on them play a particular role in the severity of tissue damage caused by the influence of these cells and therefore can be attractive targets for treatment of chronic inflammatory diseases of the respiratory organs. Siglec-8 and Siglec-10 molecules expressed on eosinophils have been actively studied in BA pathogenesis. However, given the importance of not only eosinophils, but also other cells in the disease pathogenesis, it seems challenging to investigate the role of Siglec-3, Siglec-5, Siglec-6, and Siglec-14 expressed on mast cells and basophils. In recent years, the role of Siglec-3, Siglec-9, and Siglec-5/14 has been studied in the pathogenesis of COPD. The use of antibodies against Siglec-15 described recently may be relevant in treatment of osteoporosis often associated with COPD. Based on scientific literature data, this article reviews the role of siglecs as possible regulators of inflammation in patients with chronic bronchopulmonary diseases.

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Inhaled Corticosteroids Increase Siglec-5/14 Expression in Sputum Cells of COPD Patients

Cited by 12 publications

References 15 publications

Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity

Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity

Sialic acids as cellular markers of immunomodulatory action of dexamethasone on glioma cells of different immunogenicity

Sialic Acid-Binding Lectins as Potential Pathophysiological Targets in Treatment of Chronic Bronchopulmonary Diseases (Review)

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