Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes: in vivo and in vitro studies.
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.
Department of Clinical Medicine, University of Insubria, Via Ottorino Rossi n. 9, 21100 Varese VA- Italy.
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Marino
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Guasti
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M
Cosentino
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De Piazza
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Simoni
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Bianchi
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Piantanida
F
F
Saporiti
M G
MG
Cimpanelli
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Crespi
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P
Vanoli
D
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De Palma
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Klersy
G M
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Frigo
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Bartalena
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Venco
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Lecchini
D000328:Adult; D000368:Aged; D013956:Antithyroid Agents / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology; D013963:Thyroid Hormones / Q000097:blood / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000532:radiotherapy / Q000601:surgery; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D013963:Thyroid Hormones; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019284:Thapsigargin; D013972:Thyrotropin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D013974:Thyroxine; D002118:Calcium