Mesangial cell necrosis in Thy 1 glomerulonephritis--an ultrastructural study.

Cell death is central to many physiological and pathological processes. As tissue reactions to the two forms of cell death, necrosis and apoptosis, differ, it is critical to distinguish between them. Although ultrastructure is still the definitive means of assessing this, there are very few in vivo studies. Administration of anti-Thy 1 antibody in rats is a model of acute glomerular mesangial cell death due to their expression of the Thy 1.1 epitope. The nature of this process is unclear; apoptosis was suggested from early morphological studies and recent in vitro effects of anti-Thy 1.1 antibody. We have re-examined the changes by electron microscopy, and identified a process of cell necrosis starting within 30 min of anti-Thy 1.1 antibody administration. Although there was chromatin condensation, the necrotic features distinctive from apoptosis were: loss of nuclear membranes, cell swelling and degeneration of cytoplasmic organelles, with liberation of chromatin and organelles into the interstitium causing acute inflammation without phagocytic uptake of apoptotic bodies. These findings accord with the known complement dependence of this model. Ultrastructure is a valuable means of differentiating between in vivo necrosis and apoptosis and this is important for understanding the pathogenesis of injury and subsequent tissue responses.