IFN-β, IFN-γ, and TNF-α decrease erythrophagocytosis by human monocytes independent of SIRP-α or SHP-1 expression

Abstract

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.

Conclusion: We conclude that IFN-β and IFN-γ/TNF-α decrease erythrophagocytosis by human monocytes in vitro, and this effect does not apparently require an increase in SIRP-α or SHP-1 expression.

Keywords::

• Erythrophagocytosis
• SIRP-α
• SHP-1
• cytokines
• phagocytes

Acknowledgements

We thank Walmir Cutrim Aragão Filho for the formatting of the images in this work, and BioMed Proof reading for the proof reading of the article.

Declaration of interest

This research was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).