Antitumoral properties of aged human monocytes.
It is known that older people are more sensitive to cancer and infectious agents and need more time to recover from such disorders. Can this difference in sensitivity to cancer and infections between elderly and younger people be a result of a difference in their immune systems and, more specifically, in the way monocytes react to infectious agents and cancer cells? To determine what happens after cells have aged, human monocytes were purified from young donors (approximately 25 years of age) and from older donors (65 years of age or older) and tested for their ability to respond to the polyclonal activator LPS. Our results showed that monocytes from aged donors (aged monocytes), when compared with monocytes from younger donors (young monocytes) did lose part of their cytotoxicity against tumor cells (A375 human melanoma cells and L929 murine fibroblast cells). In addition, aged monocytes displayed a sharp decrease in IL-1 secretion, but did display the intracellular 31 kDa IL-1 precursor. Moreover, aged monocytes displayed a decrease in the production of reactive oxygen intermediates such as NO2 and H2O2. Finally, aged monocytes stimulated by LPS displayed an increase in intracellular cyclic AMP and have lost their protein kinase C translocation from the cytosol to the plasma membranes. These results suggest that age affects the immunologic and antitumoral properties of human monocytes.
McLachlan
J A
JA
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Serkin
C D
CD
Morrey
K M
KM
Bakouche
O
O
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D007375:Interleukin-1; D017382:Reactive Oxygen Species; D000242:Cyclic AMP; D011493:Protein Kinase C