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 (Ca2+i) acts as a second messenger and regulates diverse functions in many cell types. The purpose of the present study...
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| Published in | Pediatrics international Vol. 51; no. 4; pp. 474 - 477 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Melbourne, Australia
Blackwell Publishing Asia
01.08.2009
Blackwell Publishing Ltd |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1328-8067 1442-200X 1442-200X |
| DOI | 10.1111/j.1442-200X.2008.02761.x |
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| Abstract | Background: Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca2+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 ([Ca2+]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca2+]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 [Ca2+]i were examined after stimulation of neutrophils with N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP).
Results: At baseline, the [Ca2+]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 [Ca2+]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 [Ca2+]i and the prolonged response of [Ca2+]i to fMLP appear to be phenotypic traits of neutrophils in subjects with DS. This suggests intrinsic cellular defects in DS. |
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| AbstractList | 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.BACKGROUNDNeutrophils 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.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).METHODSThe 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).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.RESULTSAt 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.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.CONCLUSIONSThe 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. 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. 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. 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). 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. 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. Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca2+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 ([Ca2+]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca2+]i regulation in neutrophils. 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 [Ca2+]i were examined after stimulation of neutrophils with N -formyl-methionyl-leucyl-phenylalanine (fMLP). At baseline, the [Ca2+]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 [Ca2+]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. The higher [Ca2+]i and the prolonged response of [Ca2+]i to fMLP appear to be phenotypic traits of neutrophils in subjects with DS. This suggests intrinsic cellular defects in DS. [PUBLICATION ABSTRACT] Background: Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca2+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 ([Ca2+]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca2+]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 [Ca2+]i were examined after stimulation of neutrophils with N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP). Results: At baseline, the [Ca2+]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 [Ca2+]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 [Ca2+]i and the prolonged response of [Ca2+]i to fMLP appear to be phenotypic traits of neutrophils in subjects with DS. This suggests intrinsic cellular defects in DS. AbstractBackground: Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca2+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 ([Ca2+]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca2+]i regulation in neutrophils.Methods: The study group consisted of 27 subjects with DS (age, 8.6 plus or minus 4.6 years) and 14 healthy subjects (age, 12.0 plus or minus 3.9 years). Using a fluorescent probe, fura-2, the baseline levels and changes in [Ca2+]i were examined after stimulation of neutrophils with N-formyl-methionyl-leucyl-phenylalanine (fMLP).Results: At baseline, the [Ca2+]i of neutrophils from DS subjects was significantly higher than that of the controls (70.6 plus or minus 28.0 nmol/L vs 44.4 plus or minus 16.0 nmol/L, P < 0.01). The absolute [Ca2+]i after addition of fMLP in the DS subjects was also significantly higher than that of the control group (250 plus or minus 91 nmol/L vs 167 plus or minus 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 [Ca2+]i and the prolonged response of [Ca2+]i to fMLP appear to be phenotypic traits of neutrophils in subjects with DS. This suggests intrinsic cellular defects in DS. |
| Author | Takaya, Junji Yamato, Fumiko Yasuhara, Akihiro Ikemoto, Yumiko Teraguchi, Masayuki Kaneko, Kazunari |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19400826$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1371_journal_pone_0175437 crossref_primary_10_3389_fimmu_2021_621440 crossref_primary_10_3389_fimmu_2018_03058 crossref_primary_10_1016_j_jaci_2014_07_015 crossref_primary_10_1186_s10020_018_0004_y crossref_primary_10_1111_imr_13296 crossref_primary_10_1093_hmg_dds529 crossref_primary_10_4236_ojpsych_2013_32A004 |
| Cites_doi | 10.1002/(SICI)1096-8628(19990611)84:5<406::AID-AJMG4>3.0.CO;2-4 10.1152/physrev.1993.73.3.547 10.2223/JPED.966 10.4049/jimmunol.170.1.64 10.1016/S0021-9258(19)83641-4 10.1002/neu.480230915 10.1203/00006450-198409000-00024 10.1002/mrdd.1025 10.1016/S0531-5565(01)00179-6 10.1016/S0006-2952(01)00588-3 10.1016/S0022-3476(75)80077-1 10.4049/jimmunol.125.4.1665 10.1016/S0022-1759(99)00167-2 10.1111/j.1365-2249.1997.505-ce1403.x 10.1001/jama.240.8.737b 10.1007/BF00858987 |
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| References | Hallett MB, Hodges R, Cadman M et al. Techniques for measuring and manipulating free Ca2+ in the cytosol and organelles of neutrophils. J. Immunol. Methods 1999; 232: 77-88. Proesmans W, De Cock P, Eyskens. A toddler with Down syndrome, hypercalcaemia, hypercalciuria, medullary nephrocalcinosis and renal failure. Pediatr. Nephrol. 1995; 9: 112-14. Yasui K, Shinozaki K, Nakazawa T, Agematsu K, Komiyama A. Presenility of granulocytes in Down syndrome individuals. Am. J. Med. Genet. 1999; 84: 406-12. Tam CF, Walford RL. Alterations in cyclic nucleotides and cyclase-specific activities in T lymphocytes of aging normal humans and patients with Down's syndrome. J. Immunol. 1980; 125: 1665-70. Choi DW. Excitoxic cell death. J. Neurobiol. 1992; 23: 1261-76. Tintinger GR, Theron AJ, Anderson R, Ker JA. The anti-inflammatory interactions of epinephrine with human neutrophils in vitro are achieved by cyclic AMP-mediated accelerated resequestration of cytosolic calcium. Biochem. Pharmacol. 2001; 61: 1319-28. Anderson R, Goolam Mahomed A. Calcium efflux and influx in f-met-leu-phe(fMLP)-activated human neutrophils are chronologically distinct events. Clin. Exp. Immunol. 1997; 110: 132-8. Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 1985; 260: 3440-50. Klut ME, Ruehlmann DO, Li L, Whalen BA, Van Breemen C, Hogg JC. Age-related changes in the calcium homeostasis of adherent neutrophils. Exp. Gerontol. 2002; 37: 533-41. Scharff O, Foder B. Regulation of cytosolic calcium in blood cells. Physiol. Rev. 1993; 73: 547-82. Lott IT, Head E. Down syndrome and Alzheimer's disease: A link between development and aging. Ment. Retard. Dev. Disabil. Res. Rev. 2001; 7:172-8. Cocchi P, Silenzi M, Ravina A. Neutrophil viability in Down's syndrome. JAMA 1978; 240: 737. Haslett C, Guthrie LA, Kopaniak MM, Johnston RB Jr, Henson PM. Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am. J. Pathol. 1985; 119: 101-10. Andrei LK, Howard RP. Intracellular calcium waves accompany neutrophil polarization, formylmethionylleucylphenylalanine stimulation, and phagocytosis: A high speed microscopy study. J. Immunol. 2003; 170: 64-72. Barkin RM, Weston WL, Humbert JR, Maire F. Phagocytic function in Down syndrome. Chemotaxis. J. Ment. Defic. Res. 1980; 24: 243-9. Ribeiro LM, Jacob CM, Pastorino AC, Kim CA, Fomin AB, Castro AP. Evaluation of factors associated with recurrent and/or severe infections in patients with Down's syndrome. J. Pediatr. (Rio. J.) 2003; 79: 141-8. McCoy EE, Sneddon JM. Decreased calcium content and 45 Ca2+ uptake in Down's syndrome blood platelets. Pediatr. Res. 1984; 18: 914-16. Barkin RM, Weston WL, Humbert JR, Sunada K. Phagocytic function in Down syndrome. Bactericidal activity and phagocytosis. J. Ment. Defic. Res. 1980; 24: 251-6. Khan AJ, Evans HE, Glass L, Skin YH, Almonte D. Defective neutrophil chemotaxis in patients with Down syndrome. J. Pediatr. 1975; 87: 87-9. 1995; 9 2001; 61 2002; 37 1993; 73 2001; 7 1980; 24 1997; 110 2003; 79 1978; 240 2003; 170 1984; 18 1999; 232 1999; 84 1975; 87 1985; 119 1985; 260 1992; 23 1980; 125 e_1_2_6_20_2 Haslett C (e_1_2_6_9_2) 1985; 119 e_1_2_6_8_2 Tam CF (e_1_2_6_12_2) 1980; 125 e_1_2_6_18_2 e_1_2_6_19_2 e_1_2_6_4_2 e_1_2_6_3_2 Barkin RM (e_1_2_6_6_2) 1980; 24 e_1_2_6_5_2 e_1_2_6_13_2 e_1_2_6_2_2 e_1_2_6_10_2 e_1_2_6_11_2 Barkin RM (e_1_2_6_7_2) 1980; 24 e_1_2_6_16_2 e_1_2_6_17_2 e_1_2_6_14_2 e_1_2_6_15_2 |
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Techniques for measuring and manipulating free Ca2+ in the cytosol and organelles of neutrophils. J. Immunol. Methods 1999; 232: 77-88. – reference: Barkin RM, Weston WL, Humbert JR, Maire F. Phagocytic function in Down syndrome. Chemotaxis. J. Ment. Defic. Res. 1980; 24: 243-9. – reference: Anderson R, Goolam Mahomed A. Calcium efflux and influx in f-met-leu-phe(fMLP)-activated human neutrophils are chronologically distinct events. Clin. Exp. Immunol. 1997; 110: 132-8. – reference: Klut ME, Ruehlmann DO, Li L, Whalen BA, Van Breemen C, Hogg JC. Age-related changes in the calcium homeostasis of adherent neutrophils. Exp. Gerontol. 2002; 37: 533-41. – reference: Andrei LK, Howard RP. Intracellular calcium waves accompany neutrophil polarization, formylmethionylleucylphenylalanine stimulation, and phagocytosis: A high speed microscopy study. J. Immunol. 2003; 170: 64-72. – reference: Cocchi P, Silenzi M, Ravina A. Neutrophil viability in Down's syndrome. 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| Snippet | Background: Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The... Background: Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The... Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular... AbstractBackground: Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to... |
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| SubjectTerms | Adolescent Calcium Calcium - analysis Calcium - physiology Child Child, Preschool Down syndrome Down Syndrome - metabolism Female Humans intracellular calcium Leukocytes Male neutrophil Neutrophils - chemistry Neutrophils - metabolism Pediatrics |
| Title | Elevated intracellular calcium in neutrophils in patients with Down syndrome |
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