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Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: impact on mediators and mechanisms of the inflammatory response
- Source :
- The FASEB Journal. 24:3970-3980
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
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.
- Subjects :
- Blood Platelets
Male
Settore BIO/14 - FARMACOLOGIA
lipoxin
Cystic Fibrosis Transmembrane Conductance Regulator
Apoptosis
Inflammation
Pharmacology
platelet-leukocyte interaction
Biochemistry
Cystic fibrosis
Cell Line
Nitric oxide
cystic fibrosis
chemistry.chemical_compound
Microscopy, Electron, Transmission
nitric oxide
Genetics
medicine
Humans
Platelet
Phosphorylation
Molecular Biology
Protein kinase B
Lipoxin
biology
Reverse Transcriptase Polymerase Chain Reaction
Chemistry
medicine.disease
Immunohistochemistry
Cystic fibrosis transmembrane conductance regulator
inflammation resolution
Immunology
biology.protein
Female
Inflammation Mediators
medicine.symptom
Protein Kinases
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....1da84607ac39b5c1a6332e211abfdeff