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Type: Artigo de periódico
Title: Sirp-alpha And Shp-1 Expression In Autoimmune Hemolytic Anemia [expressão De Sirp-alfa E Shp-1 Na Anemia Hemolítica Autoimmune]
Author: de Almeida A.C.
Abstract: SIRP-alpha (Signal Regulatory Protein alpha) is an inhibitory receptor on phagocytes. Its activation and consequent ITIM phosphorylation occur by binding to CD47 present in the erythrocyte membrane, thus allowing SHP-1 recruitment which dephosphorylates specific substrates involved in the mediation of varying physiologic effects. The aim of this work was to determine the role of dexamethasone and IFN-gamma/TNF-alpha on the expressions of SIRP-alpha and SHP-1 and erythrophagocytosis, as well as to evaluate the regulation of SIRP-alpha and SHP-1 in peripheral blood monocytes (PBM) of patients presenting with autoimmune hemolytic anemia (AIHA) before and after glucocorticoid therapy. PBM cells from healthy donors were cultured in dexamethasone, IFN-gamma/TNF-alpha, or Hemin. The SIRP-alpha/SHP-1 gene expressions were determined by real-time PCR, SIRP-alpha/SHP-1 protein levels were determined by western blotting, and erythrophagocytosis was determined by microscopy. In vitro, IFN-gamma/TNF-alpha increased SIRP-alpha gene and protein expressions, as well as the SHP-1 gene expression, in parallel to a decrease in erythrophagocytosis in PBM. Conversely, although the SIRP-alpha/SHP-1 gene expressions were significantly increased, dexamethasone did not alter the SIRP-alpha/SHP-1 protein expressions or erythrophagocytosis by monocytes. The SIRP-alpha/SHP-1 expressions were significantly higher in the PBM of AIHA patients compared with normal or AIHA patients after glucocorticoid therapy. Only the SIRP-alpha gene expression was increased using the hemin culture. Our results confirm the key role of SIRP-alpha in the regulation of erythrophagocytosis and suggest that the SIRPalpha gene expression in AIHA patients before glucocorticoid therapy is increased due to heme release, and the decrease in the SIRP-alpha gene expression after glucocorticoid therapy is due to the indirect effect of this drug in reducing erythrophagocytosis and heme availability.
Rights: aberto
Identifier DOI: 
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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