EXCESS FORMATION OF LYSOPHOSPHATIDIC ACID WITH AGE INHIBITS MYRISTIC ACID-INDUCED SUPEROXIDE ANION GENERATION IN INTACT HUMAN NEUTROPHILS

A superoxide anion generation rate upon exposure to myristate of 1.93/-0.34 nmol/min/10(6) cells in neutrophils from elderly human donors w as significantly less than a value of 3.02+/-0.48 nmol/min/10(6) neutr ophils from young donors, Myristate activation resulted in equal incre ases of AA in both the young and the old indicating no effect of aging on the PLA(2) pathway to response, By contrast, the PLD-induced gener ation of PA was significantly higher in the old than in the young, In addition, myristate induced a significant age-related enhancement in L PA generation, in the old but not in the young, The mass of LPA genera ted following activation was 3.5 nmol/2.5x10(7) cells/ml in the young while in the old it averaged 7.0 nmol/2.5x10(7) cells/ml. The inhibito ry effects of LPA may explain the age-related impaired ability to gene rate superoxide anion following activation by myristate.