/CXCR4ϩ cells indicating progenitor cells with the homing receptor CXCR4). Cytokine serum levels (SCF, SDF-1, VEGF, EPO, and G-CSF) were assessed using ELISA. Levels of PTH and thyroid hormone as well as serum electrolytes, renal and liver parameters, and blood count were analyzed. Our data show for the first time a significant increase of circulating BMCs and an upregulation of SDF-1 and VEGF serum levels in patients with PHPT. The number of circulating BMCs returned to control levels measured 16.7 Ϯ 2.3 mo after surgery. There was a positive correlation of PTH levels with the number of CD45ϩ /c-kit ϩ , and CD45 ϩ /CD34 ϩ /CXCR4 ϩ cells. However, there was no correlation between cytokine serum concentrations (SDF-1, VEGF) and circulating BMCs. Serum levels of G-CSF, EPO, and SCF known to mobilize BMCs were even decreased or remained unchanged, suggesting a direct effect of PTH on stem cell mobilization. Our data suggest a new function of PTH mobilizing BMCs into peripheral blood. parathyroid hormone; mobilization; cytokines BONE MARROW-DERIVED PROGENITOR CELLS (BMC) are the source of all mature blood cells. They reside in niches of bone marrow and can be released into the circulation (1, 38). Mobilization of BMC into peripheral blood occurs in response to different stimuli, including chemokines, hormones, and growth factors (2,6,11,12,14,16,19,24,32,33). Endothelial progenitor cells (EPC) are a subpopulation of BMC known to contribute to vessel formation and restoration (8,13,34,36). Mobilization of EPC can also be induced by traumatic vascular injury or other forms of physiological stress like tissue ischemia or physical exercise (9,19,28,32). Furthermore, low levels of circulating EPC represent a negative prognostic marker for cardiovascular events and subsequent death (35). In experimental and clinical trials, EPC have been used for the treatment of ischemic disease, leading to a restored blood flow, increased capillary density, and an improved cardiac function (5,7,15,17, 23,24,27,39). Besides their vasculoprotective function, EPC can also play a maladaptive role in tumor progression (17,25,26). It has been demonstrated (25, 26) that EPC may infiltrate tumors and give rise to up to 16% of the tumor neovascularization.Starting in the late 1950s, an effect of parathyroid hormone (PTH) on the hematopoietic system was shown. Administration of PTH stimulated proliferation of murine colony-forming unit spleen and bone marrow cells via cAMP, leading to an increased survival of X-irradiated mice (37). Recently, Calvi et al. (4) were able to demonstrate that PTH strengthens survival and self-renewal of hematopoietic BMC by activating osteoblasts. In addition, activated osteoblasts were shown (18, 22, 29 -31) to increase the production of growth factors known to enhance mobilization of BMC into the peripheral blood. In the present study we wanted to investigate the effect of primary hyperparathyroidism (PHPT), a condition of sustained PTH stimulation, on mobilization of BMC.
PATIENTS AND METHODS
Patients.Twenty-four...