Neutrophil apoptosis is associated with a reduction in CD16 (Fc gamma RIII) expression.
Resolution of inflammation involves removal of recruited neutrophils from inflamed sites via a noninflammatory mechanism, possibly involving neutrophil apoptosis and engulfment/phagocytosis by macrophages. In this study, we describe the reduction in surface expression (> 90%) of the neutrophil molecule Fc gamma RIII (CD16) during in vitro culture at 37 degrees C, which was found to be temporally associated with the appearance of neutrophils with apoptotic morphology during in vitro culture and inhibitable by granulocyte-macrophage colony-stimulating factor (GM-CSF), which postpones apoptosis in the neutrophil. By using dual fluorescence analysis, CD16 "low" expressing neutrophils showed reduced staining with the DNA-binding dye propidium iodide, suggesting that CD16 low expressing neutrophils were apoptotic. Separation of CD16 "high" and CD16 "low" expressing neutrophils by fluorescence-activated cell sorting revealed that morphologically apoptotic cells exhibited the CD16 low phenotype. We did not observe similar marked changes in expression of other neutrophil surface molecules (including other phosphatidylinositol (PI)-linked molecules), indicating that generalized loss of surface molecules does not occur during apoptosis. We believe this to be the first reported cell type-specific membrane alteration in a surface glycoprotein associated with apoptosis, suggesting that the program of cell death in the neutrophil, in addition to morphologic and nuclear changes, includes alterations in expression of surface receptors.
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, U.K.
I
I
Dransfield
A M
AM
Buckle
J S
JS
Savill
A
A
McDowall
C
C
Haslett
N
N
Hogg
D017209:Apoptosis; D010450:Endopeptidases / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D013696:Temperature
D017261:Glycosylphosphatidylinositols; D017452:Receptors, IgG; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010450:Endopeptidases