CD47 ligation induces a rapid caspase-independent apoptosis-like cell death in human monocytes and dendritic cells.
CD47 is a versatile cell-surface molecule expressed on nearly all haematopoietic cells. In its capacity as a thrombospondin-1 (TSP-1) receptor, CD47 has recently been shown to mediate cell death in certain cells, for example, activated but not resting T cells. Here, we have investigated the possibility that human monocytes and dendritic cells (DCs) undergo cell death, following CD47 ligation. Using the TSP-1-derived CD47-binding peptide 4N1K, we found that both freshly isolated monocytes and monocyte-derived DCs underwent a rapid, caspase-independent cell death. This was characterized by the simultaneous presence of phosphatidylserine exposure, plasma membrane permeability, reduced mitochondrial membrane potential and highly fragmented DNA. Not all cells were sensitive to 4N1K-induced apoptosis; a plateau of cell death reached at an average of 38% of the monocyte and DCs populations. The results presented here, thus, show that CD47 can mediate a rapid apoptosis-like cell death of human monocytes and DCs.
Johansson
U
U
Imperial College School of Medicine, Kennedy Institute of Rheumatology Division, Hammersmith, UK. johansson@bartsandthelondon.nhs.uk
Higginbottom
K
K
Londei
M
M
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000819:agonists / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology
C120273:4N1K peptide; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D009842:Oligopeptides; D020169:Caspases; D019204:GTP-Binding Proteins