Y. Ori et al., Impaired lymphocyte calcium metabolism in endstage renal disease: Enhancedinflux, decreased efflux, and reduced response to mitogen, J LA CL MED, 133(4), 1999, pp. 391-400
Citations number
49
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Lymphocytes from patients with end-stage renal disease (ESRD) exhibit eleva
ted cytosolic calcium concentration ((Ca2+)i), but the mechanisms responsib
le for this elevated (Ca2+)i have not been entirely elucidated. In addition
, lymphocyte proliferative responses to mitogenic stimuli are suppressed in
patients with ESRD, The objectives of the study were as follows: (1) to me
asure calcium influx and efflux in lymphocytes from patients with ESRD; (2)
to measure the effect of the calcium regulator parathyroid hormone (PTH) o
n lymphocyte (Ca2+)i; (3) to measure cytosolic calcium signal in patients'
lymphocytes after mitogenic stimulation. The three study groups were as fol
lows: healthy subjects (control), patients with chronic renal failure (CRF)
before the beginning of regular dialysis treatment, and patients undergoin
g regular hemodialysis (HD) treatment. Peripheral blood lymphocytes were te
sted in vitro for (Ca2+)i, Ca2+ influx, and membrane calcium-adenosine trip
hosphatase (CaATPase) activity. Cytosolic Ca2+ signals were traced after st
imulations by PTH and by phytohemagglutinin (PHA), Baseline (Ca2+)i was sig
nificantly elevated in both ESRD groups. Ca2+ influx was enhanced and CaATP
ase activity was reduced in both ESRD groups. PTH caused a (Ca2+)i increase
in normal cells in a dose-dependent manner. PHA caused a (Ca2+)i elevation
, with a Ca2+ signal in both groups of patients with ESRD that was signific
antly smaller than that in the control group, These findings suggest that t
he high (Ca2+)i found in lymphocytes from patients with ESRD is the result
of enhanced Ca2+ influx concomitant with reduced Ca2+ extrusion, as reflect
ed by reduced CaATPase activity. The patients' elevated serum PTH levels ma
y have contributed to the high (Ca2+)i. The impaired cytosolic [Ca2+)i resp
onse to PHA may explain in part the suppressed lymphocyte proliferative res
ponse to PHA in patients with ESRD.