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.


OBJECTIVE
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.


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.


CONCLUSIONS
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.
Centro de Investigação em Pediatria e Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil. carualmeida@gmail.com
Ana Carolina
AC
de Almeida
Soraya Massaro
SM
Barbosa
Maria
M
de Lourdes Rios Barjas-Castro
Sara Terezinha
ST
Olalla-Saad
Antonio
A
Condino-Neto
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology*; D004910:Erythrocyte Membrane / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000096:biosynthesis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000943:Antigens, Differentiation; C573415:IFNG protein, human; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6