Neutrophil apoptosis is associated with loss of signal regulatory protein alpha (SIRP alpha) from the cell surface

• 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, SIRP alpha, 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 SIRP alpha was affected during apoptosis. We found that apoptotic neutrophils lost SIRP alpha from their cell surface with kinetics similar to the loss of CD16. The majority of neutrophils with reduced SIRP alpha 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 SIRP alpha 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, SIRP alpha was also found on smaller membrane vesicles released from the cells during apoptosis. Our data suggest that neutrophils reduce their SIRP alpha expression during apoptosis, which may be part of the functional down-regulation seen in apoptotic neutrophils. J. Leukoc. Biol. 93: 403-412; 2013.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

inflammation

proteolytic shedding

Fas

caspase

CD16

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)