Neutrophil apoptosis is associated with loss of signal regulatory protein alpha (SIRPα) from the cell surface
| Autor: | Per-Arne Oldenborg, Åsa Stenberg, Janove Sehlin |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Neutrophils Immunology Cell Down-Regulation Apoptosis Inflammation CD16 GPI-Linked Proteins Hydroxamic Acids Antigen medicine Signal-regulatory protein alpha Humans Immunology and Allergy fas Receptor Receptors Immunologic Caspase Innate immune system biology Cell Membrane Receptors IgG Cell Biology Neutrophil extracellular traps Antigens Differentiation Cell biology Matrix Metalloproteinase 8 medicine.anatomical_structure biology.protein Female Matrix Metalloproteinase 3 medicine.symptom |
| Zdroj: | Journal of Leukocyte Biology. 93:403-412 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.1110637 |
| Popis: | SIRPα expression is downregulated on the cell surface of apoptotic neutrophils due to proteolytic shedding and membrane loss. Cells of the innate immune system, including monocytes, macrophages, and neutrophils, play a major role in the development of inflammatory diseases. During inflammation, large numbers of neutrophils are recruited from the blood and subsequently undergo apoptosis, which involves changes in the cell surface expression of a number of receptors. Neutrophils express the Ig superfamily member, SIRPα, which is a receptor involved in regulating cell adhesion and migration. As apoptotic neutrophils down-regulate their capacity for adhesion and migration, we here investigated whether neutrophil expression of SIRPα was affected during apoptosis. We found that apoptotic neutrophils lost SIRPα from their cell surface with kinetics similar to the loss of CD16. The majority of neutrophils with reduced SIRPα also expressed PS on their surface, and the loss of the receptor was reduced proportional to the reduction of apoptosis by caspase inhibitors during Fas-induced apoptosis but less so during spontaneous apoptosis. Neutrophil loss of SIRPα or CD16 was inhibited by the protease inhibitor TAPI-2, as well as specific inhibitors of MMP3 or -8, suggesting that proteolytic mechanisms were involved. Finally, SIRPα was also found on smaller membrane vesicles released from the cells during apoptosis. Our data suggest that neutrophils reduce their SIRPα expression during apoptosis, which may be part of the functional down-regulation seen in apoptotic neutrophils. |
| Databáze: | OpenAIRE |
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