Polymorphonuclear cell-mediated oxidative responsiveness in the elderly.

Over the last few years, an array of experimental and clinical data supports a role for free radicals in the pathogenesis of aging phenomenon. In this context, toxic oxygen metabolites released by activated polymorphonuclear cells (PMN) may in part contribute to the increased burden 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 effect, the observation of an unaffected phorbol 12-myristate 13-acetate (PMA)-induced superoxide anion (O(2)()) generation implies that other mechanisms may be involved in such a deficit. In this regard, 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 lipopolysaccharide (LPS)-priming to fully restore PMN oxidative response induced by FMLP. Finally, a beta(2) integrin-dependent defect in PMN adhesiveness has been observed as a function of age. However, in spite of this finding, the increase of O(2)() production by aged adherent cells mimicks that observed in young controls, this suggesting the possible occurrence of a prolonged O(2)() release as a consequence of the persistence of infectious agents. Taken together, these findings outline a selective dysfunction of oxidative metabolism in the elderly.