Lowering of Ameboid Microglial Resistance to Hydrogen Peroxide by Propentofylline

Employing video-enhanced contrast/differential-interference contrast (VEC-DIC) microscopy, we examined the effects of l0-5 M propentofylline on the hydrogen peroxide (H2O2)-enhanced cellular activity of ameboid microglia. The 20-min survival rate of ameboid microglia after H2O2 exposure in the control was two of two at 10-4 M, five of six at 10-3 M, one of two at 10-2 M, and none of four at 10-1 M. The value of TC50 (toxic concentration for 50% survival) was 10-2.5 M. When ameboid microglia were pretreated with propentofylline, their resistance to H2O2 was greatly decreased. Upon exposure to millimolar H2O2, the microglia exhibited drastic changes, with the immediate commencement of a large ruffling wave at the peripheral part of the lamellipodia, formation of giant phagocytic vesicles containing H2O2, rapid transportation of a phagosome to the nucleus, evacuation of its contents onto the nucleus, immediate fragmentation of the lamellipodia, and shrinkage of the nude us with condensation of chromatin. These changes usually occurred within a few minutes after exposure to H2O2. The survival rate of ameboid microglia pretreated with propentofylline was one of one at l0-7 M, three of six at 10-5 M, none of one at 10-4 M, and none of six at 10-3 M. The value of the TC50 was 10-5 M. At 10-3 M, five control cells survived, whereas all six cells pretreated with propentofylline died (P< 0.05). It was concluded, therefore, that propentofylline lowered the resistance of ameboid microglia to H2O2.