Effect of parathyroid hormone on elastase release from human polymorphonuclear leucocytes

Area of Science:

• Nephrology
• Endocrinology
• Immunology

Background:

• Renal failure is linked to secondary hyperparathyroidism and increased catabolism.
• Elevated proteolytic activity in blood is suspected in renal failure patients.
• Parathyroid hormone (PTH) may stimulate protease release due to calcium-dependent mechanisms.

Purpose of the Study:

• To investigate the effect of PTH and its fragments on elastase release from polymorphonuclear leucocytes (PMNL).
• To elucidate the mechanisms involved in PTH-induced elastase release.

Main Methods:

• Assessing elastase release from PMNL stimulated by 1-84 PTH, its fragments, and phorbol ester (PMA).
• Utilizing EDTA, verapamil, trifluoperazine, W-7, and staurosporin to explore underlying mechanisms.
• Comparing the effects of amino-terminal (1-34 PTH) and carboxyterminal (19-84 PTH) fragments.

Main Results:

• 1-84 PTH dose- and time-dependently stimulated elastase release from PMNL.
• PTH-induced elastase release was abolished by hormone inactivation and EDTA, and reduced by calcium channel blockers and calmodulin inhibitors.
• The carboxyterminal 19-84 PTH fragment significantly stimulated elastase release, while the amino-terminal 1-34 PTH did not.
• Both PTH and PMA-induced elastase release were inhibited by staurosporin, indicating protein kinase C involvement.

Conclusions:

• PTH stimulates elastase release from PMNL, suggesting a role in the proteolytic activity observed in renal failure.
• The carboxyterminal fragment of PTH is primarily responsible for this effect.
• Calcium and protein kinase C signaling pathways are implicated in PTH-mediated elastase release.