NEUTROPHIL APOPTOSIS IS ASSOCIATED WITH A REDUCTION IN CD16 (FC-GAMMA-RIII) EXPRESSION

Resolution of inflammation involves removal of recruited neutrophils f rom inflamed sites via a noninflammatory mechanism, possibly involving neutrophil apoptosis and engulfment/phagocytosis by macrophages. In t his study, we describe the reduction in surface expression (>90%) of t he neutrophil molecule Fc gamma RIII (CD16) during in vitro culture at 37 degrees C, which was found to be temporally associated with the ap pearance of neutrophils with apoptotic morphology during in vitro cult ure and inhibitable by granulocyte-macrophage colony-stimulating facto r (GM-CSF), which postpones apoptosis in the neutrophil. By using dual fluorescence analysis, CD16 ''low'' expressing neutrophils showed red uced staining with the DNA-binding dye propidium iodide, suggesting th at CD16 low expressing neutrophils were apoptotic. Separation of CD16 ''high'' and CD16 ''low'' expressing neutrophils by fluorescence-activ ated cell sorting revealed that morphologically apoptotic cells exhibi ted the CD16 low phenotype. We did not observe similar marked changes in expression of other neutrophil surface molecules (including other p hosphatidylinositol (PI)-linked molecules), indicating that generalize d loss of surface molecules does not occur during apoptosis. We believ e 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 morphologi c and nuclear changes, includes alterations in expression of surface r eceptors.