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

摘要: Inflammatory lung disease is a primary cause of morbidity and mortality in cystic fibrosis (CF). Mechanisms unresolved acute inflammation CF are not completely known, although the involvement transmembrane conductance regulator (CFTR) nonrespiratory cells emerging. Here we examined CFTR expression function human platelets (PLTs) found that they express biologically active CFTR. blockade gave an ∼50% reduction lipoxin A(4) (LXA(4)) formation during PLT/polymorphonuclear leukocytes (PMN) coincubations by inhibiting synthase activity PLT 12-lipoxygenase. PLTs from patients generated ∼40% less LXA(4) compared to healthy subject PLTs. 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 0.11±0.002 pmol/10(8) PLTs; P=0.004), while reducing AKT (1.02±0.12 0.71±0.007 U; P=0.04), increasing p38 MAPK phosphorylation (0.650±0.09 1.04±0.24 P=0.03). Taken together, these findings indicate affected molecular defect Moreover, this abnormality may explain failure resolution CF.