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Elevated intracellular calcium in neutrophils in patients with Down syndrome
Author(s) -
Yamato Fumiko,
Takaya Junji,
Yasuhara Akihiro,
Teraguchi Masayuki,
Ikemoto Yumiko,
Kaneko Kazunari
Publication year - 2009
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/j.1442-200x.2008.02761.x
Subject(s) - medicine , intracellular , calcium , endocrinology , calcium in biology , stimulation , second messenger system , fura 2 , neutrophile , immunology , receptor , biochemistry , enzyme , biology , inflammation , cytosol
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.