title: Neutrophil apoptosis is associated with loss of signal regulatory protein alpha (SIRPα) from the cell surface.
abstract: 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.
authors.affiliation: Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umea University, Umea, Sweden.
authors.forename: Asa
authors.initials: A
authors.lastname: Stenberg
authors.forename: Janove
authors.initials: J
authors.lastname: Sehlin
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000276:immunology / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000276:immunology / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C491901:FAS protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D006877:Hydroxamic Acids; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; C099410:TAPI-2; D019014:fas Receptor; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8