Early damage of sympathetic neurons after co-culture with macrophages: a model of neuronal injury in vitro

Since activated immune cells may damage peripheral nerves during inflammati on, we developed a co-culture model that permits the direct study of macrop hage-induced neuronal damage. Sympathetic neurons were enzymatically isolat ed from neonatal mice and co-cultured with increasing numbers of peritoneal macrophages for 24 h. This caused rapid neuronal cell death, reducing neur onal number by 24.1+/-4% with the addition of 11.5 x 10(3) macrophages, rep resenting a ratio of 8 macrophages per neuron. Nuclear analysis showed that cell death occurred by both apoptosis and necrosis. These effects were not mimicked by addition of macrophage-conditioned medium, and were prevented by 10 mu M dexamethasone. Although no appreciable neuronal death occurred b eyond 24 h, the density of neurites was decreased between 1 and 2 days of c o-culture (p<0.05). There is, therefore, a rapid induction of cytotoxicity by macrophages after their addition to the neuronal cultures, followed by a xonal damage without neuronal cell death. NeuroReport 11:177-181 (C) 2000 L ippincott Williams & Wilkins.