Open Access

The effects of disodium pamidronate on human polymorphonuclear leukocytes and platelets: An in vitro study

  • Eleonora Salvolini1Email author,
  • Monia Orciani1,
  • Arianna Vignini2,
  • Roberto Di Primio1 and
  • Laura Mazzanti2
Cellular & Molecular Biology LettersAn International Journal200914:12

DOI: 10.2478/s11658-009-0012-6

Received: 22 September 2008

Accepted: 16 February 2009

Published: 23 February 2009

Abstract

Recent reports have indicated that, as well as having antiresorptive effects, bisphosphonates could have an application as anti-inflammatory drugs. Our aim was to investigate whether this anti-inflammatory action could be mediated by the nitric oxide (NO) released by the leukocytes migrating to the site of inflammation. In particular, we investigated in vitro the intracellular calcium concentration ([Ca2+]i), the level of NO released by PMN and platelets, and the PMN myeloperoxidase activity after incubation with disodium pamidronate, since there was a postulated modulatory effect of this aminosubstituted bisphosphonate on leukocytes both in vitro and in vivo. Our data shows that the pamidronate treatment provoked a significant increase in the [Ca2+]i parallel to the enhancement in NO release, suggesting a possible activation of constitutive nitric oxide synthase, while the myeloperoxidase activity was significantly reduced. In conclusion, we hypothesized that treatment with pamidronate could stimulate NO-production by cells present near the bone compartment, thus constituting a protective mechanism against bone resorption occurring during inflammation. In addition, PMN- and platelet-derived NO could act as a negative feed-back signal to restrict the inflammatory processes.

Key words

Pamidronate Polymorphonuclear leukocytes Platelets Nitric oxide Intracellular calcium Myeloperoxidase activity

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