Effect of parathyroid hormone on human T cell activation

Klinger, Marian; Alexiewicz, Jadwiga M.; Linker‐Israeli, Mariana; Pitts, Thomas O.; Gaciong, Zbigniew; Fadda, George Z.; Massry, Shaul G.

doi:10.1038/ki.1990.147

Cited by 76 publications

(48 citation statements)

References 50 publications

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“…Klinger et al [33] found that in hemodialysis patients, parathormone augmented T-cell proliferation induced by PHA as well as interleukin 2 production by these cells [34], CAPD patients lose macrophages and proteins in cluding immunoglobulins with the peritoneal effluent [35]. The loss of immunoglobulins represents about 15 % of the total amount of proteins.…”

Section: Discussionmentioning

confidence: 99%

Varicella-Zoster Virus Immune Status in CAPD and Chronic Hemodialysis Patients

Smetana

Leventon-Kriss²,

Broide³

et al. 1991

Am J Nephrol

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Patients on chronic dialysis who are supposed to disclose an impairment of the immune potential, seldom show clinical viral illnesses. Since severe varicella-zoster virus (VZV) infection develops in immunocompromised patients, we have examined the proliferative activity to VZV in the blood lymphocytes of 16 patients on continuous ambulatory peritoneal dialysis (CAPD) and compared it to healthy matched controls. The cellular in vitro response of these patients to specific VZV antigens was essentially normal. The mean stimulation index for CAPD patients was 7.06, and for matched controls 3.68 (p > 0.05). The mean percentage of lymphocytes in CAPD patients as determined by CD₃ monoclonal antibodies was 57%, the CD₄ helper and CD₈ suppressor cells were 41 and 21 %, respectively. When those 16 CAPD patients were followed up for the presence of anti-VZV IgA, IgM and IgG immunofluorescent antibody to membrane antigen antibodies during a period of 6 months, the recrudescence of VZV was documented by the appearance of IgA and IgM antibodies and/or fourfold increase in IgG titer in some patients, but no clinical illness was observed. The frequent reactivation of the virus without clinical symptoms in patients undergoing long-term intermittent chronic hemodialysis (HD) or CAPD was strengthened by the presence of increased anti-VZV geometric mean titers (52.68 and 53.00, respectively) in these patients as compared to control subjects (11.75).

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Section: Discussionmentioning

confidence: 99%

Varicella-Zoster Virus Immune Status in CAPD and Chronic Hemodialysis Patients

Smetana

Leventon-Kriss²,

Broide³

et al. 1991

Am J Nephrol

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“…Patients with renal failure-related hyperparathyroidism have impaired humoral immunity, including reduced B cell proliferation and antibody production [43]. Lymphocytes have receptors for PTH [44], and it has been reported that PTH inhibits production of IgG, IgA and IgM by cultured human B cells, while the inactivation of PTH abolishes this inhibitory effect [45]. The respective contributions of these various mechanisms to immune dysfunction in patients with hyperparathyroidism need to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 production and secretion by human parathyroids

Safley¹,

Villinger

Jackson³

et al. 2004

Clinical and Experimental Immunology

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SUMMARYParathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection of parathyroid tumours. Because IL-6 is also expressed in normal parathyroids and in other endocrine cells (adrenal and islet), we hypothesized that parathyroid tumours might contribute directly to the elevated serum IL-6 levels in patients with hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, and chromogranin-A (an endocrine and neuroendocrine tumour marker) in normal, adenomatous and hyperplastic parathyroids. Using immunofluorescence and confocal microscopy, IL-6 co-localized with PTH and with chromogranin-A in parathyroid cells. All cultured parathyroid tumours secreted IL-6 at levels markedly higher than optimally stimulated peripheral blood mononuclear cells. Supernates from cultured parathyroids stimulated proliferation of an IL-6-dependent cell line, and anti-IL-6 MoAb abolished this stimulatory effect. IL-6 mRNA was documented in cultured parathyroid tumours, cultured normal parathyroids, fresh operative parathyroid tumours and fresh operative normal specimens. In conclusion, these data show that parathyroid tumours and normal parathyroids contain, produce and secrete IL-6. Our findings present a novel pathway by which human parathyroids may contribute markedly to IL-6 production and elevation of serum IL-6 levels in patients with hyperparathyroidism. The physiological relevance of IL-6 production by human parathyroids remains to be determined, but IL-6 secretion by parathyroid tumours may contribute to bone loss and to other multi-system complaints observed in these patients.

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“…In 65,115,116 (ii) elevated [Ca 2+ ] i and total Ca 2+ concentration of PBMC in response to ALDOST and which occurs before tissue invasion, together with increased H 2 O 2 production by monocytes and lymphocytes; 65 (iii) PTH regulated T-cell activation; [117][118][119][120] (iv) parathyroidectomy prevented PBMC Ca 2+ overloading and vascular lesions; 83,84 (v) upregulated expression of antioxidant defenses in these cells; and (vi) prevention of Ca 2+ loading and oxi/nitrosative stress by cotreatment with either Spiro or an antioxidant. 13,65,116 The presence of oxi/nitrosative stress at a systemic level in these models is evidenced by increased serum levels of thiobarbituric acid-reacting substances and reduced activity of plasma a 1 -antiproteinase.…”

Section: Cellular and Molecular Pathways Leading To Proinflammatory Cmentioning

confidence: 99%

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

et al. 2010

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Inappropriately (relative to dietary Na + ) elevated plasma aldosterone concentrations (PAC), or aldosteronism, have been incriminated in both the appearance of the cardiometabolic syndrome (CMS) and its progressive nature. The deleterious dual consequences of elevated PAC and dietary Na + have been linked to several components of the CMS, including salt-sensitive hypertension. Moreover, their adverse consequences are considered to be synergistic, culminating in a pro-oxidant phenotype with oxidative injury involving the heart and systemic tissues, including peripheral blood mononuclear cells (PBMC). Our experimental studies in rats receiving aldosterone/salt treatment have identified a common pathogenic event that links aldosteronism to the induction of oxidative stress. Herein, we review these findings and the important role of excessive intracellular Ca 2+ accumulation (EICA), or intracellular Ca 2+ overloading, which occurs in the heart and PBMC, leading to, respectively, cardiomyocyte necrosis with a replacement fibrosis and an immunostimulatory state with consequent coronary vasculopathy. The origin of EICA is based on elevations in plasma parathyroid hormone, which are integral to the genesis of secondary hyperparathyroidism that accompanies aldosteronism and occurs in response to plasma-ionized hypocalcemia and hypomagnesemia whose appearance is the consequence of marked urinary and fecal excretory losses of Ca 2+ and Mg 2+ . In addition, we found intracellular Ca 2+ overloading to be intrinsically coupled to a dyshomeostasis of intracellular Zn 2+ , which together regulate the redox state of cardiac myocytes and mitochondria via the induction of oxidative stress and generation of antioxidant defenses, respectively. To validate our hypothesis, a series of site-directed, sequential pharmacological and/or nutriceutical interventions targeted along cellular-molecular cascades were carried out to either block downstream events leading to the pro-oxidant phenotype or to enhance antioxidant defenses. In each case, the interventions were found to be cardioprotective. These cumulative salutary responses raise the prospect that pharmacological agents and nutriceuticals capable of influencing extra-and intracellular Ca 2+ and Zn 2+ equilibrium could prevent adverse cardiac remodeling and thereby enhance the management of aldosteronism.

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Effect of parathyroid hormone on human T cell activation

Cited by 76 publications

References 50 publications

Varicella-Zoster Virus Immune Status in CAPD and Chronic Hemodialysis Patients

Varicella-Zoster Virus Immune Status in CAPD and Chronic Hemodialysis Patients

Interleukin-6 production and secretion by human parathyroids

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

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