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.
Klut
M E
ME
McDonald Research Laboratories/iCAPTURE Centre, The University of British Columbia, St Paul's Hospital, 1081 Burrad, Vancouver BC, Canada V6Z 1Y6. mklut@mrl.ubc.ca
Ruehlmann
D O
DO
Li
L
L
Whalen
B A
BA
Van Breemen
C
C
Hogg
J C
JC
D000328:Adult; D000367:Age Factors; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005434:Flow Cytometry; D006706:Homeostasis; D006801:Humans; D018613:Microscopy, Confocal; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*
D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium