Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes: in vivo and in vitro studies

Int J Immunopathol Pharmacol. Jan-Mar 2006;19(1):149-60.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antithyroid Agents / therapeutic use
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Female
  • Humans
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Male
  • Middle Aged
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Thapsigargin / pharmacology
  • Thyroid Hormones / blood
  • Thyroid Hormones / pharmacology*
  • Thyroid Neoplasms / radiotherapy
  • Thyroid Neoplasms / surgery
  • Thyroidectomy
  • Thyrotropin / blood
  • Thyrotropin / pharmacology*
  • Thyroxine / pharmacology
  • Uncoupling Agents / pharmacology

Substances

  • Antithyroid Agents
  • Iodine Radioisotopes
  • Thyroid Hormones
  • Uncoupling Agents
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • N-Formylmethionine Leucyl-Phenylalanine
  • Thapsigargin
  • Thyrotropin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Thyroxine
  • Calcium