CHANGES IN APOPTOSIS OF HUMAN POLYMORPHONUCLEAR GRANULOCYTES WITH AGING

Many alterations with aging occur at the cellular and organic levels i n the immune system ultimately leading to a decrease in the immune res ponse. Our aim in the present work was to study apoptosis of polymorph onuclear granulocytes (PMN) with aging under various stimulations sinc e apoptosis might play an important role in several pathologies encoun tered with aging. The PMN of healthy young (20-25 years) and elderly ( 65-85 years) subjects were examined after 24 h of sterile culture with and without stimulation. The stimulating agents included: phorbol myr istate acetate (PMA), hydrogen peroxide (H2O2), N-formyl-methionyl-leu cyl phenylalanine (FMLP), granulocyte-macrophage colony stimulating fa ctor (GM-CSF), reduced glutathione (GSH), lipopolysaccharide (LPS) and interleukin 2 (IL-2). Apoptosis was assessed by traditional staining of the plates, by flow cytometric staining and DNA gel electrophoresis . It was found that without stimulation the susceptibility of PMN to a poptosis was slightly increased with aging. Under various stimulations , such as PMA, H2O2, apoptosis was almost 100%, while the treatment by FMLP, oxLDL and GSH did not change its extent in PMN obtained either from young or elderly subjects. Marked age-related changes were observ ed in the extent of apoptosis under stimulation with GM-CSF, IL-2 and LPS. These agents were able to significantly prevent apoptosis in PMN of young subjects, while only the GM-CSF was able to slightly modulate it in neutrophils of elderly subjects. From these results, we suggest that changes in apoptosis of PMN with aging could play a role in the increased incidence of certain immune system related pathologies of ag ing, such as cancer, infections and autoimmune disorders. (C) 1997 Els evier Science Ireland Ltd.