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.
Marino
F
F
Department of Clinical Medicine, University of Insubria, Via Ottorino Rossi n. 9, 21100 Varese VA- Italy.
Guasti
L
L
Cosentino
M
M
De Piazza
D
D
Simoni
C
C
Bianchi
V
V
Piantanida
E
E
Saporiti
F
F
Cimpanelli
M G
MG
Crespi
C
C
Vanoli
P
P
De Palma
D
D
Klersy
C
C
Frigo
G M
GM
Bartalena
L
L
Venco
A
A
Lecchini
S
S
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