APOPTOTIC CELL-DEATH OF A HYBRID MOTONEURON CELL-LINE INDUCED BY IMMUNOGLOBULINS FROM PATIENTS WITH AMYOTROPHIC-LATERAL-SCLEROSIS

Apoptotic cell death has recently been implicated in diseases involvin g nonproliferating, terminally differentiated cells such as neurons. P revious experiments have documented that immunoglobulins from patients with amyotrophic lateral sclerosis (ALS) can kill motoneuron-neurobla stoma hybrid cells [ventral spinal cord 4.1 (VSC 4.1)] by a calcium-de pendent process. Here, we studied the mechanism of ALS IgG-induced cel l death. In the presence of ALS IgG the VSC 4.1 cells undergo cell shr inkage and membrane blebbing, which are morphological features of apop totic cell death. The damaged cells can be identified by in situ end l abeling of nicked DNA and biochemically show laddering on agarose gel electrophoresis. This ALS IgG-triggered process is prevented by cycloh eximide, aurintricarboxylic acid, and zinc sulfate. These dais demonst rate that immunoglobulins from patients with ALS are able to induce ap optosis in motoneuron hybrid cells and provide a potential mechanism f or motoneuron degeneration in human ALS.