The parathyroid hormone-2 receptor is expressed on human leukocytes and down-regulated in hyperparathyroidism.
BACKGROUND
Parathyroid hormone (PTH) has specific effects on function, migration and proliferation of human leukocytes. These effects may contribute to accelerated atherosclerosis and impaired immune response observed in patients with renal insufficiency. Recently, a new G protein-coupled receptor with substantial implications for vascular function--the PTH2 receptor (PTH2-R)--has been identified, however, expression and distribution in humans and a possible regulation has not yet been studied. We therefore investigated the expression of the PTH2 receptor on human leukocytes in healthy subjects and in patients with hyperparathyroidism.


METHODS
PTH2 receptor expression was quantified by flow cytometry (FACS) analysis on monocytes, lymphocytes and granulocytes that were isolated from peripheral blood (hypotonic density gradient centrifugation) and by immunohistochemistry using a specific alpha-PTH2-R antibody produced in rabbit. Results of 22 patients with hyperparathyroidism (12 renal allograft recipients, 10 hemodialysis patients, mean age 43 +/- 8 years) were compared to 22 age and sex-matched healthy controls.


RESULTS
Mean relative antigen density of the PTH2 receptor and percentage of positive cells in healthy subjects was 19 +/- 5 and 90 +/- 6% on granulocytes, 5 +/- 2 and 55 +/- 19% on monocytes, and 24 +/- 7 and 21 +/- 7% on lymphocytes. In patients with hyperparathyroidism, mean antigen density was significantly lower on granulocytes and monocytes (17 +/- 4% and 3 +/- 1%, p < 0.01, respectively). The percentage of positive cells and mean expression on lymphocytes was not significantly different. A significant and inverse correlation was found between plasma PTH concentrations and the mean PTH2 receptor expression on granulocytes (r = -0.41, p < 0.05).


CONCLUSIONS
The PTH2 receptor is expressed on human granulocytes and--to a lesser degree--on monocytes and lymphocytes. In patients with hyperparathyroidism the PTH2 receptor is down-regulated as function of plasma PTH levels.
Seeliger
S
S
Department of Paediatrics, University Hospital Münster, Germany.
Hausberg
M
M
Eue
I
I
Usdin
T
T
Rahn
K H
KH
Kosch
M
M
D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism*; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D044183:Receptor, Parathyroid Hormone, Type 2; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*
D044183:Receptor, Parathyroid Hormone, Type 2; D018016:Receptors, Parathyroid Hormone