Chronic Granulomatous Disease: From Genetic Defect to Clinical Presentation

Bylund, Johan; Green, David; Speert, David P.

doi:10.1007/0-387-25342-4_5

Cited by 36 publications

(42 citation statements)

References 108 publications

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“…54 Although the basis of increased inflammatory cell influx into the lungs of NADPH oxidase-deficient mice is not yet clear, a possible explanation of this finding is that there is an accumulation of ingested particles that cannot be phagositized, and/or decreased apoptosis in inflammatory cells, both of which are attributable to the defect in NADPH oxidase functioning. 55,56 Furthermore, the increased inflammatory cell migration into the lung tissue of NADPH oxidase-deficient mice could be a source of the higher cytokine and chemokine release, which in turn could attract more peripheral monocytes and neutrophils into the lungs in response to CS exposure. 5,21 It is interesting to note that the neutrophil infiltration and the levels of proinflammatory mediators in the lungs were decreased in subchronic CS-exposed mice as compared to acute CS-exposed mice, which corroborates our recent observation showing a similar biphasic proinflammatory mediator release in rat lungs after CS exposure.…”

Section: Discussionmentioning

confidence: 99%

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Yao

Edirisinghe

Yang

et al. 2008

The American Journal of Pathology

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Cigarette smoke (CS) induces recruitment of inflammatory cells in the lungs leading to the generation of reactive oxygen species (ROS), which are involved in lung inflammation and injury. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a multimeric system that is responsible for ROS production in mammalian cells. We hypothesized that NADPH oxidase-derived ROS play an important role in lung inflammation and injury and that targeted ablation of components of NADPH oxidase (p47 phox and gp91 phox ) would protect lungs against the detrimental effects of CS. To test this hypothesis, we exposed p47 phox؊/؊ and gp91 phox؊/؊ mice to CS and examined inflammatory response and injury in the lung. Surprisingly, although CS-induced ROS production was decreased in the lungs of p47 phox؊/؊ and gp91 phox؊/؊ mice compared with wild-type mice, the inflammatory response was significantly increased and was accompanied by development of distal airspace enlargement and alveolar destruction. This pathological abnormality was associated with enhanced activation of the TLR4-nuclear factor-B pathway in response to CS exposure in p47 phox؊/؊ and gp91 phox؊/؊ mice. This phenomenon was confirmed by in vitro studies in which treatment of peritoneal macrophages with a nuclear factor-B inhibitor reversed the CS-induced release of proinflammatory mediators. Thus, these data suggest that genetic ablation of components of NADPH oxidase enhances susceptibility to the proinflammatory effects of CS leading to airspace enlargement and alveolar damage.

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Section: Discussionmentioning

confidence: 99%

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Yao

Edirisinghe

Yang

et al. 2008

The American Journal of Pathology

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“…The molecular weight of the core oligosaccharide was calculated from electrospray ionization-MS data obtained in our laboratory on the core extracted from a clinical strain of B. cepacia. 4 Since both lipid A and core moieties showed a certain degree of structural variability, the mean molecular weight was evaluated, taking into account all the molecular masses obtained by MS analyses for both species. The mass spectra exhibited a single peak for each species present; the peak intensity was taken as the relative occurrence of each molecular species.…”

Section: Methodsmentioning

confidence: 99%

“…BCC species were initially described as plant pathogens (1), but all species have the ability to cause serious infections in patients with cystic fibrosis (CF) or chronic granulomatous disease (CGD) (2). These two disease conditions are quite disparate, CF being caused by dysfunctional chloride transport in the lung epithelium (3) and CGD being caused by an inability of phagocytes to generate the reactive oxygen species (ROS) important for microbial killing (4). However, they may share features explaining the virulence of BCC in these particular patient groups.…”

mentioning

confidence: 99%

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

Bylund

Burgess

Cescutti

et al. 2006

Journal of Biological Chemistry

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135

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Bacteria belonging to the Burkholderia cepacia complex are important opportunistic pathogens in compromised hosts, particularly patients with cystic fibrosis or chronic granulomatous disease. Isolates of B. cepacia complex may produce large amounts of exopolysaccharides (EPS) that endow the bacteria with a mucoid phenotype and appear to facilitate bacterial persistence during infection. We showed that EPS from a clinical B. cenocepacia isolate interfered with the function of human neutrophils in vitro; it inhibited chemotaxis and production of reactive oxygen species (ROS), both essential components of innate neutrophil-mediated host defenses. These inhibitory effects were not due to cytotoxicity or interference with intracellular calcium signaling. EPS also inhibited enzymatic generation of ROS in cell-free systems, indicating that it scavenges these bactericidal products. B. cenocepacia EPS is structurally distinct from Pseudomonas aeruginosa alginate, yet they share the capacity to scavenge ROS and inhibit chemotaxis. These properties could explain why the two bacterial species resist clearance from the infected cystic fibrosis lung.

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“…This phagocyte accumulation reflects the inability of these cells to kill ingested pathogens or undergo apoptosis, due to defective NOX2 activity. 12,13 The role of NOX has also been well established under nonpathological conditions. Vascular NOX generate ROS important for maintaining normal cardiovascular health through the regulation of blood pressure, which is essential to health, as aberrations from normal levels can be lethal.…”

Section: Introductionmentioning

confidence: 99%

NADPH oxidases: an overview from structure to innate immunity-associated pathologies

et al. 2014

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Chronic Granulomatous Disease: From Genetic Defect to Clinical Presentation

Cited by 36 publications

References 108 publications

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Exopolysaccharides from Burkholderia cenocepacia Inhibit Neutrophil Chemotaxis and Scavenge Reactive Oxygen Species

NADPH oxidases: an overview from structure to innate immunity-associated pathologies

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