AGE-RELATED-CHANGES IN NEUTROPHIL STRUCTURE AND FUNCTION

The elderly suffer higher rates of morbidity and mortality from infectious disease than younger adults. Since neutrophils are the first line of defense against infection the vulnerability to infection of the elderly may be due, at least in part, to age-related changes in neutrophils (PMNs). Previous studies have suggested that there is an age-related increase in plasma membrane microviscosity in lymphocytes and neurons of the elderly. We have explored the hypothesis that there is a similar change in plasma membrane viscosity in the neutrophil and that this alteration in the neutrophil plasma membrane leads to diminished neutrophil function. When we studied plasma membrane viscosity of neutrophils by determining the fluorescence anisotropy of 1-(4-trimethylaminophenyl)-6-diphenyl-1,3,5-hexatriene labeled cells, we were surprised to find that plasma membrane viscosity is decreased in the neutrophils of the elderly as compared to young controls (microviscosity parameter, 1.33 +/- 0.07, in the elderly, n = 21, versus 1.62 +/- 0.06, in young controls, n = 19, P < 0.004). As expected, stimulated (FMLP 0.1-mu-M) O2- generation by neutrophils from the elderly was significantly decreased compared with young controls (34 +/- 7% decrease, n = 6, P < 0.04). Both resting and stimulated neutrophils demonstrated an age-related decline in adherence to a component of the extracellular matrix, denatured collagen (gelatin, P < 0.04, n = 22 elderly subjects). In contrast, neutrophils from the elderly adhered to fibrinogen at least as well as neutrophils from young controls. Moreover, chemotaxis to activated complement components (in zymosan activated plasma) and FMLP did not change with increased age whether studied in the Boyden chamber (92 +/- 7% control, n = 14) or under agarose (90 +/- 13% control, n = 11). These studies suggest that an age-related decrease in plasma membrane viscosity is associated with a decrease in O2- production and adherence of neutrophils to components of the extracellular matrix. Thus, age-related alterations in neutrophil structure may result in diminished neutrophil function and increased susceptibility to infection with pyogenic bacteria.