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

Raimondo De Cristofaro, Bianca Rocca, Giovanna Petrucci, Stefano Lancellotti, D Mattoscio, V Evangelista, A Recchiuti, A Pandolfi, S Di Silvestre, S Manarini, N Martelli, Df Angelini, L Battistini, I Robuffo, T Pensabene, L Pieroni, Ml Furnari, F Pardo, S Quattrucci, G DavìM. Romano

Risultato della ricerca: Contributo in rivistaArticolo in rivista

59 Citazioni (Scopus)

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 A(4) (LXA(4)) formation during PLT/polymorphonuclear leukocytes (PMN) coincubations by inhibiting the lipoxin synthase activity of PLT 12-lipoxygenase. PLTs from CF patients generated ∼40% less LXA(4) 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/10(8) 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.
Lingua originaleEnglish
pagine (da-a)3970-3980
Numero di pagine11
RivistaFASEB JOURNAL
Volume24
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Blood Platelets
  • Inflammation Mediators
  • cystic fibrosis

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