TY - JOUR
T1 - Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes
T2 - In vivo and in vitro studies
AU - Marino, F.
AU - Guasti, L.
AU - Cosentino, M.
AU - De Piazza, D.
AU - Simoni, C.
AU - Bianchi, V.
AU - Piantanida, E.
AU - Saporiti, F.
AU - Cimpanelli, M. G.
AU - Crespi, C.
AU - Vanoli, P.
AU - De Palma, D.
AU - Klersy, C.
AU - Frigo, G. M.
AU - Bartalena, L.
AU - Venco, A.
AU - Lecchini, S.
PY - 2006/1
Y1 - 2006/1
N2 - Intracellular free calcium concentrations ([Ca++]i) were studied in polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice, when hypothyroid (visit 1) and after restoration of euthyroidism by L-T4 TSH-suppressive therapy (visit 2). PMNs from patients at visit 1 had significantly lower resting [Ca++]i levels compared to both visit 2 and controls. Values at visit 2 did not differ from those of the controls. Stimulus-induced [Ca++]i rise was also significantly blunted at visit 1 and normalized at visit 2, possibly through a differential contribution of distinct intracellular Ca++ stores, as suggested by the response pattern to the chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy subjects with high TSH concentrations impaired intracellular Ca++ store function. Both resting [Ca++]i levels and fMLP-induced [Ca++]i rise increased in the presence either of low-concentration TSH or of T4, but effects of TSH and T4 were not additive. T3, rT3, and TRIAC had no effect. In conclusion, this study provides evidence for a direct relationship between thyroid status and [Ca++]i homeostasis in human PMNs, mainly related to direct actions of TSH and T4 on these cells.
AB - Intracellular free calcium concentrations ([Ca++]i) were studied in polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice, when hypothyroid (visit 1) and after restoration of euthyroidism by L-T4 TSH-suppressive therapy (visit 2). PMNs from patients at visit 1 had significantly lower resting [Ca++]i levels compared to both visit 2 and controls. Values at visit 2 did not differ from those of the controls. Stimulus-induced [Ca++]i rise was also significantly blunted at visit 1 and normalized at visit 2, possibly through a differential contribution of distinct intracellular Ca++ stores, as suggested by the response pattern to the chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy subjects with high TSH concentrations impaired intracellular Ca++ store function. Both resting [Ca++]i levels and fMLP-induced [Ca++]i rise increased in the presence either of low-concentration TSH or of T4, but effects of TSH and T4 were not additive. T3, rT3, and TRIAC had no effect. In conclusion, this study provides evidence for a direct relationship between thyroid status and [Ca++]i homeostasis in human PMNs, mainly related to direct actions of TSH and T4 on these cells.
KW - Hypothyroidism
KW - Intracellular free calcium concentrations
KW - L-thyroxine replacement
KW - Polymorphonuclear leukocytes
KW - Thyroid hormones
UR - http://www.scopus.com/inward/record.url?scp=33646232955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646232955&partnerID=8YFLogxK
M3 - Article
C2 - 16569353
AN - SCOPUS:33646232955
VL - 19
SP - 149
EP - 160
JO - International Journal of Immunopathology and Pharmacology
JF - International Journal of Immunopathology and Pharmacology
SN - 0394-6320
IS - 1
ER -