Ligation of CD47 during monocyte differentiation into dendritic cells results in reduced capacity for interleukin-12 production.
We have previously shown that the CD47-binding thrombospondin-1 (TSP-1)-derived peptide 4N1K induces a rapid apoptosis-like death of human monocytes and dendritic cells (DCs). However, not all cells were susceptible to the peptide-induced cell death and here, we have investigated whether surviving monocytes could differentiate into functionally normal DCs. We found that the cell-surface phenotype, the T-cell stimulatory capacity and the ability to undergo lipopolysaccharide (LPS)-induced maturation into CD83+ DCs were essentially identical in 4N1K-derived and control DCs. Interleukin-10 (IL-10) production was also normal, but a significant downregulation of the pro-inflammatory cytokines IL-12 and tumour necrosis factor-alpha (TNF-alpha) was observed in the 4N1K-derived DCs. To the contrary, simultaneous stimulation of control DCs with 4N1K and LPS + interferon-gamma did not alter IL-12 production. These results indicate that although activation of the TSP-1-binding region of CD47 on monocytes induces apoptosis in a large proportion of the cells, it does not hamper the overall capacity of the surviving cells to differentiate into DCs. Such DCs, however, have a reduced capacity for IL-12 and TNF-alpha production, and the possibility that this is linked to the uptake of apoptotic cells is discussed.
Johansson
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U
Imperial College School of Medicine, Kennedy Institute of Rheumatology Division, Hammersmith, London, UK. johansson@bartsandthelondon.nhs.uk
Londei
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M
D000691:Anabasine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000819:agonists / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
C116666:3-(4-hydroxy-2-methoxybenzylidene)anabaseine; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D000691:Anabasine