MESANGIAL CELL APOPTOSIS - THE MAJOR MECHANISM FOR RESOLUTION OF GLOMERULAR HYPERCELLULARITY IN EXPERIMENTAL MESANGIAL PROLIFERATIVE NEPHRITIS

Increases in mesangial cell number may herald glomerular scarring, but they are not irreversible. This study sought mechanisms by which surp lus glomerular mesangial cells can be cleared. A small proportion of c ultured mesangial cells exhibited typical morphological features of ap optosis (programmed cell death), which was increased by growth factor deprivation or exposure to cycloheximide, stimuli known to increase ap optosis in other cell types. Apoptosis was confirmed by typical intern ucleosomal chromatin cleavage. In vivo, clear morphological evidence o f mesangial apoptosis leading to phagocytosis by neighboring mesangial cells was obtained in self-limited mesangial proliferation induced in rats by Thy1.1 antibody, apoptosis occurring similar to 10-fold more frequently than in the healthy rat glomerulus. Indeed, changes in glom erular cell number in Thy1.1 nephritis strongly suggested that apoptos is is the major cell clearance mechanism counterbalancing cell divisio n, thereby mediating resolution of glomerular hypercellularity in expe rimental mesangial proliferation.