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

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.

Abbreviations

APD:

disodium pamidronate

BP:

bisphosphonates

[Ca2+]i :

intracellular calcium concentration

MPO:

myeloperoxidase

PMN:

polymorphonuclear leukocytes

ROS:

reactive oxygen species

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Correspondence to Eleonora Salvolini.

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Salvolini, E., Orciani, M., Vignini, A. et al. The effects of disodium pamidronate on human polymorphonuclear leukocytes and platelets: An in vitro study. Cell Mol Biol Lett 14, 457–465 (2009). https://doi.org/10.2478/s11658-009-0012-6

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  • DOI: https://doi.org/10.2478/s11658-009-0012-6

Key words

  • Pamidronate
  • Polymorphonuclear leukocytes
  • Platelets
  • Nitric oxide
  • Intracellular calcium
  • Myeloperoxidase activity