Effect of Parathyroid Hormone on Random Migration of Human Polymorphonuclear Leukocytes

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Abstract
Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1–84 PTH but not its amino-terminal (1–34 PTH) or its carboxy-terminal (53–84 PTH) fragments produced marked and significant (p < 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1–84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p < 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16–20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p < 0.01) reduced and there was a significant (p < 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure. The data show that (1) PMNL are target cells for intact 1–84 PTH; (2) the effect of PTH on PMNL migration is specific to the hormone and is related to its biological activity; (3) this action of the hormone is not mediated by calcium influx into PMNL nor by stimulation of cAMP or cGMP production in these cells but may be due to redistribution of cytosolic calcium between various cell organelles; (4) prolonged exposure to intact PTH may adversely affect random migration of PMNL, and (5) the migration of PMNL is impaired in most patients with chronic renal failure and it is inversely related to serum levels of PTH. The data are consistent with the notion that the state of secondary hyperparathyroidism of chronic renal failure is responsible for altered PMNL migration and assign a new dimension for PTH toxicity in these patients.