AGE-RELATED-CHANGES IN NONRECEPTOR DEPENDENT GENERATION OF REACTIVE OXYGEN SPECIES FROM PHAGOCYTES OF HEALTHY-ADULTS

Several authors have shown that neutrophil generation of reactive oxyg en species (ROS) declines with advancing age. Similar changes have als o been suggested in monocytes. In both cases alterations in second mes senger activity have been implicated as the most likely explanation fo r these observations. The aim of this study was to investigate the eff ect of age on phagocyte ROS generation, stimulated by the direct activ ation of protein kinase C (PKC). Venous blood was drawn from normal he althy subjects, cells were separated on a double density gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate acet ate (PMA) was employed as a cell stimulus. Superoxide generation was m easured by cytochrome c reduction and myeloperoxidase (MPO) products b y measurement of peak luminol chemiluminescence (CL). Fifty-eight subj ects, 25 males and 33 females, were studied, median age 49 years (rang e 26-88 years). Polymorphonuclear cell superoxide generation was signi ficantly higher in males and there was a trend towards higher pmn MPO product generation in males. Using Spearman's ranked correlation coeff icient, monocyte superoxide generation was negatively correlated with age (r = -0.473, P < 0.001). No changes in the generation of MPO produ cts was found. There were also trends towards a negative correlation o f pmn cytochrome c reduction and peak luminol CL with age in males but not females. Since PMA directly activates protein kinase C, reduced m onocyte superoxide generation with increasing age appears to be relate d to alterations in the ROS generating system downstream of the cell r eceptor. Impaired monocyte superoxide generation may have implications for non-specific defence against certain infections and early tumour growth in the elderly. Factors underlying these changes in monocyte fu nction therefore require further study. (C) 1997 Elsevier Science Irel and Ltd.