Inflammation Research

, Volume 63, Issue 7, pp 539–547

Rapid shedding of proinflammatory microparticles by human mononuclear cells exposed to cigarette smoke is dependent on Ca2+ mobilization

  • Cinzia Cordazzo
  • Silvia Petrini
  • Tommaso Neri
  • Stefania Lombardi
  • Yuri Carmazzi
  • Roberto Pedrinelli
  • Pierluigi Paggiaro
  • Alessandro Celi
Original Research Paper

Abstract

Objectives

Microparticles are membrane vesicles shed by cells upon activation and apoptosis. Agonists capable of inducing microparticle generation include cytokines, bacterial products, P-selectin, histamine. Cigarette smoke extract has also been recognized as an agonist involved in microparticle generation with an apoptosis-dependent mechanism. We investigated the possibility that cigarette smoke extract induces the rapid generation of proinflammatory microparticles by human mononuclear cells with a calcium-dependent mechanism.

Materials and methods

Human mononuclear cells were exposed to cigarette smoke extract. [Ca2+]i mobilization was assessed with the fluorescent probe Fluo-4 NW. Microparticles were quantified with a prothrombinase assay and by flow cytometry. Normal human bronchial epithelial cells and A549 alveolar cells were incubated with cigarette smoke extract-induced microparticles and the generation of ICAM-1, IL-8, and MCP-1 was assessed by ELISA.

Results

Exposure to cigarette smoke extract induced a rapid increase in [Ca2+]i mobilization. Microparticle generation was also increased. EGTA, verapamil and the calmodulin inhibitor, W-7, inhibited microparticle generation. Incubation of lung epithelial cells with cigarette smoke extract-induced microparticles increased the expression of proinflammatory mediators.

Conclusions

Exposure of mononuclear cells to cigarette smoke extract causes a rapid shedding of microparticles with a proinflammatory potential that might add to the mechanisms of disease from tobacco use.

Keywords

Ca2+ mobilization Cigarette smoke extract Lung inflammation Microparticles 

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Cinzia Cordazzo
    • 1
    • 2
  • Silvia Petrini
    • 1
  • Tommaso Neri
    • 1
  • Stefania Lombardi
    • 3
  • Yuri Carmazzi
    • 1
  • Roberto Pedrinelli
    • 1
    • 2
  • Pierluigi Paggiaro
    • 1
  • Alessandro Celi
    • 1
  1. 1.Laboratory of Respiratory Cell Biology, Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area CriticaUniversity of Pisa and Azienda Ospedaliero-Universitaria PisanaPisaItaly
  2. 2.Istituto Nazionale di Ricerche CardiovascolariBolognaItaly
  3. 3.SSD Immunologia, Allergologia e Patologia MolecolareMassa e CarraraItaly

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