Immune elimination of aging platelets by autologous monocytes: role of membrane-specific autoantibody.

Abstract

Membrane-bound IgG was found only on old populations of platelets from normal individuals. This IgG could be dissociated from senescent cells by repeatedly heating the cells. Heat-eluted IgG (He-IgG) prepared from senescent red blood cells was capable of binding to either heat-treated old platelets or Vibrio cholerae neuraminidase (VCN)-treated young platelets, suggesting expression of a common age-dependent antigen on the senescent red blood cells and old platelets. We analyzed the role of membrane-bound IgG in the immune elimination of aging platelets by direct phagocytosis of different platelet subpopulations by autologous monocytes in vitro. While removal of He-IgG from old platelets inhibited their phagocytosis, preincubation of either heat-treated old or VCN-treated young platelets promoted phagocytosis of these cells by autologous monocytes. The phagocytosis of senescent cells required intact IgG on these cells. Either removal of Fc fragments from He-IgG or treatment of autologous monocytes with Fc fragments prior to the phagocytosis assay resulted in a marked reduction of phagocytosis (greater than 75%). We conclude that Fc receptors on the monocytes and the presence of membrane-specific IgG are crucial elements for immune elimination of senescent platelets.