Ifn-β, Ifn-γ, And Tnf-α Decrease Erythrophagocytosis By Human Monocytes Independent Of Sirp-α Or Shp-1 Expression

Background: Many cases of autoimmune hemolytic anemia have been reported after viral infection. Phagocyte activation and accompanying erythrophagocytosis are thought to result from proinflammatory cytokines released during viral infection. SIRP-α (signal regulatory protein-α), a receptor expressed on phagocytes, inhibits phagocytosis when bound to CD47 on the erythrocyte membrane. Ligation with CD47 results in SHP-1 recruitment to SIRP-α and dephosphorylation of specific downstream substrates involved in phagocytosis. SIRP-α ligation by CD47 may be inhibited by proinflammatory cytokines. Objectives: The aim of this work was to evaluate the effect of IFN-β, IFN-γ, and TNF-α on erythrophagocytosis and assess the effect on expression of SIRP-α and SHP-1 in human monocytes. Materials and methods: Monocytes were cultured ex vivo with IFN-β or IFN-γ/TNF-α. Erythrophagocytosis was determined by flow cytometry. SIRP-α and SHP-1 gene expression was determined by real time-PCR, while SIRP-α and SHP-1 protein expression was determined by western blot. Results: Erythrophagocytosis by monocytes significantly decreased after treatment with either IFN-β or IFN-γ/TNF-α. Monocytes cultured with IFN-γ/TNF-α showed increased SIRP-α gene and protein expression and SHP-1 gene expression. Monocytes cultured with IFN-β did not show any alteration in SIRP-α or SHP-1 expression. 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