Age-related changes in the calcium homeostasis of adherent neutrophils

The elderly are susceptible to infections and show a decline in neutrophil (PMN) functions that are regulated by cytosolic calcium [Ca2+]i. This study measures [Ca2+]i in suspended and adherent PMN of young and elderly individuals by using flow cytometry, confocal microscopy, the bacterial peptide fMLP, and the fluorescent Ca2+ indicator fluor-3/acettoxymethyl ester. PMN from both age groups show a steep and transient fMLP-induced Ca2+ increase. This increase is independent of external divalent cations and is desensitized by a subsequent exposure to the same agonist. Adherent PMN of the elderly express elevated [Ca2+]i before (basal) and after fMLP activation but show reduced ability to mobilize Ca2+ into and from the cytosol. PMN of the elderly take longer (13.7 +/- 3 s) to attain the maximal response compared to those of young adults (5.7 +/- 0.8 s). PMN from both age groups show heterogeneity in the time and magnitude of this response. However, PMN of the elderly show a decrease in the proportion of cells with prompt and effective reaction and an increase in the representation of a cell subpopulation manifesting delayed response. We conclude that age-related delayed and reduced PMN response to a bacterial peptide could hamper functional activities that are essential in host protection against infections.