PHOTOACTIVATED INHIBITION OF SUPEROXIDE GENERATION AND PROTEIN-KINASE-C ACTIVITY IN NEUTROPHILS BY BLEPHARISMIN, A PROTOZOAN PHOTODYNAMICALLY ACTIVE PIGMENT

Blepharismin is an endogenous photosensitizing pigment found in the pr otozoan Blepharisma. This pigment inhibited the generation of superoxi de anion (O(2)(r)adical anion) in neutrophils not only via a diacylgly cerol-induced protein kinase C (PKC)-dependent reaction but also by an arachidonate-induced PKC-independent reaction. The inhibition was lig ht and concentration dependent for both reactions. Light-activated inh ibition was strong at wavelengths between 520 and 570 nm but not above 610 nm. PKC activity in neutrophils and from rat brain was inhibited by blepharismin in a light- and concentration-dependent manner. Moreov er, arachidonate-activated NADPH oxidase activity in a cell-free syste m was also inhibited by the pigment in a light- and concentration-depe ndent manner. These results suggest that blepharismin inhibits NADPH o xidase activation through the non-specific inhibition of Various membr ane-bound enzymes and that this inhibition may also be correlated with that of PKC.