The elderly exhibit an increased propensity to suffer from a wide variety of infectious diseases as compared to younger adults. As phagocytic cells play an important role in the control of infections, a number of in vitro studies have explored possible mechanisms to account for this well documented observation. Their findings, not surprisingly, are variable, depanding on experimental conditions. For example, some reports find decreased O2 Generation from fMLP- stimulated neutrophils from elderly subjects as compared to younger adults, while with other stimuli, modest decreases, no significant change or enhancement in O2 generation has been found. The problem, of course, is a lack of accurate in vivo markers of phagocytic activity - free radical production - correlated with diminished host immune response in the elderly. In the past few years, nitric oxide (NO), from murine phagocytes, has been shown to exhibit microbicidal activity towards a number of intracellular pathogens. Considering NO is generated in an invironment where phagocytic cells produce O2 and other reduction products of O2 potential outcomes are unclear. How the free radical chemistry of these and similar reactions impact host immune response remains undefined. This is particularly important since inflammatory molecules, which often control phagocytic production of free radicals, are often elevated in the sera of the lederly. The OBJECTIVE of this research is to identify free radical formation during inflammation and quantify specific free radicals as a function of age in mice using EPR spectroscopy in combination with spin trapping. As this grant is for one year, the Specific Aim to be addressed is to in vivo in situ detect and quantitate NO and HO in senescent mice in real time at the site where the free radicals evolve using a novel low frequency EPR sectrometer and spin traps.
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