Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: Impact on mediators and mechanisms of the inflammatory response

Domenico Mattoscio, Virgilio Evangelista, Raimondo De Cristofaro, Antonio Recchiuti, Assunta Pandolfi, Sara Di Silvestre, Stefano Manarini, Nicola Martelli, Bianca Rocca, Giovanna Petrucci, Daniela F. Angelini, Luca Battistini, Iole Robuffo, Tiziana Pensabene, Luisa Pieroni, Maria Lucia Furnari, Francesca Pardo, Serena Quattrucci, Stefano Lancellotti, Giovanni DavìMario Romano

Research output: Contribution to journalArticle

Abstract

Inflammatory lung disease is a primary cause of morbidity and mortality in cystic fibrosis (CF). Mechanisms of unresolved acute inflammation in CF are not completely known, although the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in nonrespiratory cells is emerging. Here we examined CFTR expression and function in human platelets (PLTs) and found that they express a biologically active CFTR. CFTR blockade gave an ∼50% reduction in lipoxin A4 (LXA4) formation during PLT/polymorphonuclear leukocytes (PMN) coincubations by inhibiting the lipoxin synthase activity of PLT 12-lipoxygenase. PLTs from CF patients generated ∼40% less LXA4 compared to healthy subject PLTs. CFTR inhibition increased PLT-dependent PMN viability (33.0±5.7 vs. 61.2±8.2%; P=0.033), suppressed nitric oxide generation (0.23±0.04 vs. 0.11±0.002 pmol/108 PLTs; P=0.004), while reducing AKT (1.02±0.12 vs. 0.71±0.007 U; P=0.04), and increasing p38 MAPK phosphorylation (0.650±0.09 vs. 1.04±0.24 U; P=0.03). Taken together, these findings indicate that PLTs from CF patients are affected by the molecular defect of CFTR. Moreover, this CF PLT abnormality may explain the failure of resolution in CF.

Original languageEnglish
Pages (from-to)3970-3980
Number of pages11
JournalFASEB Journal
Volume24
Issue number10
DOIs
Publication statusPublished - 2010

Keywords

  • Inflammation resolution
  • Lipoxin
  • Nitric oxide
  • Platelet-leukocyte interaction

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

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  • Cite this

    Mattoscio, D., Evangelista, V., De Cristofaro, R., Recchiuti, A., Pandolfi, A., Di Silvestre, S., Manarini, S., Martelli, N., Rocca, B., Petrucci, G., Angelini, D. F., Battistini, L., Robuffo, I., Pensabene, T., Pieroni, L., Furnari, M. L., Pardo, F., Quattrucci, S., Lancellotti, S., ... Romano, M. (2010). Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: Impact on mediators and mechanisms of the inflammatory response. FASEB Journal, 24(10), 3970-3980. https://doi.org/10.1096/fj.10-159921