Elevated intracellular calcium in neutrophils in patients with Down syndrome.
BACKGROUND
Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca(2+)i) acts as a second messenger and regulates diverse functions in many cell types. The purpose of the present study was to compare the intracellular calcium concentration ([Ca(2+)]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca(2+)]i regulation in neutrophils.


METHODS
The study group consisted of 27 subjects with DS (age, 8.6 +/- 4.6 years) and 14 healthy subjects (age, 12.0 +/- 3.9 years). Using a fluorescent probe, fura-2, the baseline levels and changes in [Ca(2+)]i were examined after stimulation of neutrophils with N-formyl-methionyl-leucyl-phenylalanine (fMLP).


RESULTS
At baseline, the [Ca(2+)]i of neutrophils from DS subjects was significantly higher than that of the controls (70.6 +/- 28.0 nmol/L vs 44.4 +/- 16.0 nmol/L, P < 0.01). The absolute [Ca(2+)]i after addition of fMLP in the DS subjects was also significantly higher than that of the control group (250 +/- 91 nmol/L vs 167 +/- 60 nmol/L, respectively: P < 0.01). The neutrophils from the DS subjects had a consistently and significantly prolonged response to fMLP as compared to the neutrophils of control subjects.


CONCLUSIONS
The higher [Ca(2+)]i and the prolonged response of [Ca(2+)]i to fMLP appear to be phenotypic traits of neutrophils in subjects with DS. This suggests intrinsic cellular defects in DS.
Yamato
Fumiko
F
Department of Pediatrics, Kansai Medical University, Osaka, Japan. fkotekote@yahoo.co.jp
Takaya
Junji
J
Yasuhara
Akihiro
A
Teraguchi
Masayuki
M
Ikemoto
Yumiko
Y
Kaneko
Kazunari
K
D000293:Adolescent; D002118:Calcium / Q000032:analysis* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000737:chemistry* / Q000378:metabolism
D002118:Calcium