Regulation of neutrophil FcgammaRIIIb (CD16) surface expression following delayed apoptosis in response to GM-CSF and sodium butyrate.
When neutrophils undergo apoptosis, they lose expression of the surface receptor CD16 (FcgammaRIIIb). Thus levels of surface CD16 are good indicators of apoptotic or non-apoptotic neutrophils. Shedding of CD16 occurs via the activity of a metalloproteinase that cleaves the receptor from the plasma membrane. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and sodium butyrate both stimulate neutrophil gene expression, protect these cells from apoptosis, and maintain expression of surface CD16. In this report we have investigated whether these agents maintain surface expression of CD16 via (1) decreased shedding (2) increased mobilization of the internal pool of pre-formed CD16, or (3) via de novo biosynthesis of new receptor molecules. Although GM-CSF and sodium butyrate both preserved surface expression of CD16, GM-CSF actually accelerated the rate of shedding of this receptor. Maintenance of surface levels was achieved by substantial mobilization of the internal pool of CD16. Sodium butyrate, on the other hand, maintained surface expression without extensive store depletion via a mechanism that appeared to involve a decreased rate of shedding. In these experiments we could find no evidence for de novo biosynthesis of CD16 stimulated by either GM-CSF or sodium butyrate. These experiments indicate that multiple mechanisms exist for the maintenance of surface CD16 during rescue of neutrophils from apoptosis by different agents.
Moulding
D A
DA
School of Biological Sciences, University of Liverpool, United Kingdom.
Hart
C A
CA
Edwards
S W
SW
D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis / Q000097:blood / Q000235:genetics*; D013997:Time Factors
D002087:Butyrates; D012333:RNA, Messenger; D017452:Receptors, IgG; D016178:Granulocyte-Macrophage Colony-Stimulating Factor