POLYMORPHONUCLEAR CELL-MEDIATED OXIDATIVE RESPONSIVENESS IN THE ELDERLY

Over the last few years, an array of experimental and clinical data su pports a role for free radicals in the pathogenesis of aging phenomeno n. In this context, toxic oxygen metabolites released by activated pol ymorphonuclear cells (PMN) may in part contribute to the increased bur den of oxidants with advancing age. As far as PMN respiratory burst is concerned, many reports point out an age-related impairment of formyl peptide (FMLP)-triggered oxidative response. Although an imbalance in cell calcium homeostasis has been suggested to account for such an ef fect. the observation of an unaffected phorbol 12-myristate 13-acetate (PMA)-induced superoxide anion (O-2(radical-anion)) generation implie s that other mechanisms may be involved in such a deficit. In this reg ard, the reduction of membrane microviscosity and/or the cytoskeleton- mediated decrease of FMLP receptor expression may play a pivotal role. In addition, the latter mechanism may also explain the failure of lip opolysaccharide (LPS)-priming to fully restore PMN oxidative response induced by FMLP. Finally, a beta(2) integrin-dependent defect in PMN a dhesiveness has been observed as a function of age. However, in spite of this finding, the increase of O-2(radical-anion) production by aged adherent cells mimicks that observed in young controls, this suggesti ng the possible occurrence of a prolonged O-2(radical-anion) release a s a consequence of the persistence of infectious agents. Taken togethe r, these findings outline a selective dysfunction of oxidative metabol ism in the elderly.