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Galectin-3 Mediates NETosis and Acts as an Autoantigen in Systemic Lupus Erythematosus-Associated Diffuse Alveolar Haemorrhage.
Chen, Shih-Yao; Wang, Chung-Teng; Chen, Ching-Yi; Kuo, Pin-Yu; Wang, Chrong-Reen; Shiau, Ai-Li; Chang, Cheng-Hsi; Wu, Chao-Liang.
Afiliación
  • Chen SY; Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan.
  • Wang CT; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.
  • Chen CY; Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Kuo PY; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Wang CR; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.
  • Shiau AL; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.
  • Chang CH; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan.
  • Wu CL; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.
Int J Mol Sci ; 24(11)2023 May 30.
Article en En | MEDLINE | ID: mdl-37298447
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with enhanced NETosis and impaired degradation of neutrophil extracellular traps (NETs). Galectin-3 is a ß-galactoside binding protein and is associated with neutrophil functions as well as involved in mediating autoimmune disorders. In this study, we plan to examine the associations of galectin-3 with the pathogenesis of SLE and NETosis. Galectin-3 expression levels were determined in peripheral blood mononuclear cells (PBMCs) of SLE patients for the association with lupus nephritis (LN) or correlation of SLE disease activity index 2000 (SLEDAI-2K). NETosis was observed in human normal and SLE and murine galectin-3 knockout (Gal-3 KO) neutrophils. Gal-3 KO and wild-type (WT) mice induced by pristane were used to evaluate disease signs, including diffuse alveolar haemorrhage (DAH), LN, proteinuria, anti-ribonucleoprotein (RNP) antibody, citrullinated histone 3 (CitH3) levels, and NETosis. Galectin-3 levels are higher in PBMCs of SLE patients compared with normal donors and positively correlated with LN or SLEDAI-2K. Gal-3 KO mice have higher percent survival and lower DAH, LN proteinuria, and anti-RNP antibody levels than WT mice induced by pristane. NETosis and citH3 levels are reduced in Gal-3 KO neutrophils. Furthermore, galectin-3 resides in NETs while human neutrophils undergo NETosis. Galectin-3-associated immune complex deposition can be observed in NETs from spontaneously NETotic cells of SLE patients. In this study, we provide clinical relevance of galectin-3 to the lupus phenotypes and the underlying mechanisms of galectin-3-mediated NETosis for developing novel therapeutic strategies targeting galectin-3 for SLE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nefritis Lúpica / Trampas Extracelulares / Lupus Eritematoso Sistémico Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nefritis Lúpica / Trampas Extracelulares / Lupus Eritematoso Sistémico Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza