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-alpha (signal regulatory protein-alpha), 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-alpha and dephosphorylation of specific downstream substrates involved in phagocytosis. SIRP-alpha ligation by CD47 may be inhibited by proinflammatory cytokines. Objectives: The aim of this work was to evaluate the effect of IFN-beta, IFN-gamma, and TNF-alpha on erythrophagocytosis and assess the effect on expression of SIRP-alpha and SHP-1 in human monocytes. Materials and methods: Monocytes were cultured ex vivo with IFN-beta or IFN-gamma/TNF-alpha. Erythrophagocytosis was determined by flow cytometry. SIRP-alpha and SHP-1 gene expression was determined by real time-PCR, while SIRP-alpha and SHP-1 protein expression was determined by western blot. Results: Erythrophagocytosis by monocytes significantly decreased after treatment with either IFN-beta or IFN-gamma/TNF-alpha. Monocytes cultured with IFN-gamma/TNF-alpha showed increased SIRP-alpha gene and protein expression and SHP-1 gene expression. Monocytes cultured with IFN-beta did not show any alteration in SIRP-alpha or SHP-1 expression. Conclusion: We conclude that IFN-beta and IFN-gamma/TNF-alpha decrease erythrophagocytosis by human monocytes in vitro, and this effect does not apparently require an increase in SIRP-alpha or SHP-1 expression.