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Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: impact on mediators and mechanisms of the inflammatory response
Author(s) -
Mattoscio Domenico,
Evangelista Virgilio,
De Cristofaro Raimondo,
Recchiuti Antonio,
Pandolfi Assunta,
Di Silvestre Sara,
Manarini Stefano,
Martelli Nicola,
Rocca Bianca,
Petrucci Giovanna,
Angelini Daniela F.,
Battistini Luca,
Robuffo Iole,
Pensabene Tiziana,
Pieron Luisa,
Furnari Maria Lucia,
Pardo Francesca,
Quattrucci Serena,
Lancellotti Stefano,
Davì Giovanni,
Romano Mario
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-159921
Subject(s) - cystic fibrosis transmembrane conductance regulator , cystic fibrosis , platelet , lipoxin , chemistry , inflammation , endocrinology , medicine , immunology
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 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.—Mattoscio, D., Evangelista, V., De Cristofaro, R., Recchiuti, A., Pandolfi, A., Di Silvestre, S., Manarini, S., Martelli, N., Rocca, B., Petrucci, B., Angelini, D.F., Battistini, L., Robuffo, I., Pensabene, T., Pieroni, L., Furnari, M.L., Pardo, F., Quattrucci, S., Lancellotti, S., Davi, G., Romano, M. Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: impact on mediators and mechanisms of the inflammatory response. FASEB J. 24, 3970–3980 (2010). www.fasebj.org