The effects of disodium pamidronate on human polymorphonuclear leukocytes and platelets: an in vitro study.
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.
Salvolini
Eleonora
E
Department of Molecular Pathology and Innovative Therapies - Histology, Polytechnic University of Marche, Via Tronto 10/A, 60020, Ancona, Italy. e.salvolini@univpm.it
Orciani
Monia
M
Vignini
Arianna
A
Di Primio
Roberto
R
Mazzanti
Laura
L
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D000077268:Pamidronate; D009195:Peroxidase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004164:Diphosphonates; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D000077268:Pamidronate; D002118:Calcium