Cystic fibrosis year in review 2016

Savant, Adrienne P.; McColley, Susanna A.

doi:10.1002/ppul.23747

Cited by 11 publications

(10 citation statements)

References 89 publications

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“…Besides these organs, the abundant secretion of dehydrated mucins in CF (Henderson et al, 2014) affects the digestive and reproductive organs, and glandular ducts (Wang et al, 2014;Wiencek and Lo, 2018). The pulmonary damage is the major cause of morbidity and mortality in CF patients (Savant and McColley, 2017). A vicious cycle of persistent inflammation and infections affects severely the pulmonary parenchyma (Nichols and Chmiel, 2015).…”

Section: Introductionmentioning

confidence: 99%

Extracellular pH and lung infections in cystic fibrosis

Massip-Copiz

Santa‐Coloma

2018

European Journal of Cell Biology

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Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR mutations. It is characterized by high NaCl concentration in sweat and the production of a thick and sticky mucus, occluding secretory ducts, intestine and airways, accompanied by chronic inflammation and infections of the lungs. This causes a progressive and lethal decline in lung function. Therefore, finding the mechanisms driving the high susceptibility to lung infections has been a key issue. For decades the prevalent hypothesis was that a reduced airway surface liquid (ASL) volume and composition, and the consequent increased mucus concentration (dehydration), create an environment favoring infections. However, a few years ago, in a pig model of CF, the Na/K concentrations and the ASL volume were found intact. Immediately a different hypothesis arose, postulating a reduced ASL pH as the cause for the increased susceptibility to infections, due to a diminished bicarbonate secretion through CFTR. Noteworthy, a recent report found normal ASL pH values in CF children and in cultured primary airway cells, challenging the ASL pH hypothesis. On the other hand, recent evidences revitalized the hypothesis of a reduced ASL secretion. Thus, the role of the ASL pH in the CF is still a controversial matter. In this review we discuss the basis that sustain the role of CFTR in modulating the extracellular pH, and the recent results sustaining the different points of view. Finding the mechanisms of CFTR signaling that determine the susceptibility to infections is crucial to understand the pathophysiology of CF and related lung diseases.

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Section: Introductionmentioning

confidence: 99%

Extracellular pH and lung infections in cystic fibrosis

Massip-Copiz

Santa‐Coloma

2018

European Journal of Cell Biology

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“…P . aeruginosa is the most prevalent chronic infection that contributes to the pathogenesis of cystic fibrosis [26] , [27] . The lung injury observed in these patients involves direct destructive effects induced by the pathogen on lung parenchyma.…”

Section: Resultsmentioning

confidence: 99%

“…PA is a facultative pathogen, which frequently infects immunocompromized patients [4] , [27] . It is one of the rare bacterial species carrying a LOX gene and uniquely the corresponding enzyme is secreted into the extracellular space [5] .…”

Section: Discussionmentioning

confidence: 99%

Specific oxygenation of plasma membrane phospholipids by Pseudomonas aeruginosa lipoxygenase induces structural and functional alterations in mammalian cells

Aldrovandi

Banthiya

Meckelmann

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Pseudomonas aeruginosa is a gram-negative pathogen, which causes life-threatening infections in immunocompromized patients. These bacteria express a secreted lipoxygenase (PA-LOX), which oxygenates free arachidonic acid to 15S-hydro(pero)xyeicosatetraenoic acid. It binds phospholipids at its active site and physically interacts with lipid vesicles. When incubated with red blood cells membrane lipids are oxidized and hemolysis is induced but the structures of the oxygenated membrane lipids have not been determined. Using a lipidomic approach, we analyzed the formation of oxidized phospholipids generated during the in vitro incubation of recombinant PA-LOX with human erythrocytes and cultured human lung epithelial cells. Precursor scanning of lipid extracts prepared from these cells followed by multiple reaction monitoring and MS/MS analysis revealed a complex mixture of oxidation products. For human red blood cells this mixture comprised forty different phosphatidylethanolamine and phosphatidylcholine species carrying oxidized fatty acid residues, such as hydroxy-octadecadienoic acids, hydroxy- and keto-eicosatetraenoic acid, hydroxy-docosahexaenoic acid as well as oxygenated derivatives of less frequently occurring polyenoic fatty acids. Similar oxygenation products were also detected when cultured lung epithelial cells were employed but here the amounts of oxygenated lipids were smaller and under identical experimental conditions we did not detect major signs of cell lysis. However, live imaging indicated an impaired capacity for trypan blue exclusion and an augmented mitosis rate. Taken together these data indicate that PA-LOX can oxidize the membrane lipids of eukaryotic cells and that the functional consequences of this reaction strongly depend on the cell type.

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“…In 1993, a gene therapy clinical trial was performed. The first trial focused on the nasal epithelium and adenovirus vectors containing the CFTR gene was used in an attempt to restore CFTR function (1,(94)(95)(96)(97). The rationale behind this method was to restore the dysfunctional gene or to supplement the patient with the corrected version of the protein prior to irreversible damage (95,98,99).…”

Section: Clinical Applications Of Cf-associated Moleculesmentioning

confidence: 99%

Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review)

Tao

Sui

et al. 2020

Mol Med Rep

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Cystic fibrosis (CF) is a chronic disease causing severe impairment to the respiratory system and digestive tracts. Currently, CF is incurable. As an autosomal recessive disorder, the morbidity of CF is significantly higher among Caucasians of European descent, whereas it is less pervasive among African and Asian populations. The disease is caused by identical mutations (homozygosity) or different mutations (heterozygosity) of an autosomal recessive mutation at position 7q31.2-q31.1 of chromosome 7. Diagnostic criteria and guidelines work concurrently with laboratory detection to facilitate precise CF detection. With technological advances, the understanding of CF pathogenesis has reached an unprecedented level, allowing for increasingly precise carrier screening, more effective early stage CF intervention and improved prognostic outcomes. These advances significantly increase the life quality and expectancy of patients with CF. Given the numerous improvements in the field of CF, the current review summarized the technical advances in the study of the molecular mechanisms underlying CF, as well as how these improvements facilitate the clinical outcomes of CF. Furthermore, challenges and obstacles to overcome are discussed.

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Cystic fibrosis year in review 2016

Abstract: In this article, we highlight cystic fibrosis (CF) research and case reports published in Pediatric Pulmonology during 2016. We also include articles from a variety of journals that are thematically related to these articles, or are of special interest to clinicians.

Cited by 11 publications

References 89 publications

Extracellular pH and lung infections in cystic fibrosis

Extracellular pH and lung infections in cystic fibrosis

Specific oxygenation of plasma membrane phospholipids by Pseudomonas aeruginosa lipoxygenase induces structural and functional alterations in mammalian cells

Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review)

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