Neutrophil chemotaxis in acutely infected and clinically stable cystic fibrosis patients*

Şener, Burçin; Hasçelik, Gülşen; Özçeli̇k, Uğur; Günalp, A; Göçmen, A

doi:10.1046/j.1442-200x.1999.01116.x

Cited by 9 publications

(9 citation statements)

References 15 publications

(32 reference statements)

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“…PMN migratory responses are reduced during disease exacerbation10 which may explain the apparent difference between the clinically stable children in this study and those reported by Dai and colleagues 7. Notably, the migratory responses to fMLP have been consistently reported as being the same.…”

Section: Discussioncontrasting

confidence: 43%

Directed neutrophil migration to IL-8 is increased in cystic fibrosis: a study of the effect of erythromycin

Brennan¹,

Cooper²,

Sly³

2001

Thorax

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Background-The aim of this study was to compare neutrophil migration in cystic fibrosis (CF) and non-CF populations and to investigate the eVect of erythromycin on directed migration of neutrophils (PMNs) in CF. Methods-PMNs were isolated and their migratory capacity in response to interleukin-8 (IL-8) or f-Met-Leu-Phe (fMLP) in the presence or absence of erythromycin (1-100 µg/ml) was assessed. Results-CF derived PMNs showed significantly increased migration to IL-8 but not to fMLP compared with non-CF PMNs. Erythromycin had no significant eVect on migration responses to IL-8 and in vitro exposure of PMNs to erythromycin had no eVect. Conclusions-CF derived PMNs show higher migratory responsiveness to IL-8 but not to fMLP, suggesting that CF PMNs may be "primed" to IL-8 which is significantly increased in CF serum compared with non-CF serum. Treatment with erythromycin had no significant eVect on PMN migration in vitro. (Thorax 2001;56:62-64)

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Section: Discussioncontrasting

confidence: 43%

Directed neutrophil migration to IL-8 is increased in cystic fibrosis: a study of the effect of erythromycin

Brennan¹,

Cooper²,

Sly³

2001

Thorax

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“…Observations of neutrophil inflammation in CF infants, where no pathogens were detected, have been challenged by evidence showing colonization of the lower respiratory tract at subclinical levels before presentation of symptoms (13). An in vitro study has shown a significant decrease in directed chemotaxis between neutrophils isolated from healthy individuals and from acutely infected CF patients (48). These studies, however, were unable to sufficiently answer the complex questions surrounding neutrophil recruitment to an infection.…”

Section: Discussionmentioning

confidence: 99%

Specific Resistance to Pseudomonas aeruginosa Infection in Zebrafish Is Mediated by the Cystic Fibrosis Transmembrane Conductance Regulator

et al. 2010

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Cystic fibrosis (CF) is a genetic disease caused by recessive mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is associated with prevalent and chronic Pseudomonas aeruginosa lung infections. Despite numerous studies that have sought to elucidate the role of CFTR in the innate immune response, the links between CFTR, innate immunity, and P. aeruginosa infection remain unclear. The present work highlights the zebrafish as a powerful model organism for human infectious disease, particularly infection by P. aeruginosa. Zebrafish embryos with reduced expression of the cftr gene (Cftr morphants) exhibited reduced respiratory burst response and directed neutrophil migration, supporting a connection between cftr and the innate immune response. Cftr morphants were infected with P. aeruginosa or other bacterial species that are commonly associated with infections in CF patients, including Burkholderia cenocepacia, Haemophilus influenzae, and Staphylococcus aureus. Intriguingly, the bacterial burden of P. aeruginosa was found to be significantly higher in zebrafish Cftr morphants than in controls, but this phenomenon was not observed with the other bacterial species. Bacterial burden in Cftr morphants infected with a P. aeruginosa ⌬LasR mutant, a quorum sensing-deficient strain, was comparable to that in control fish, indicating that the regulation of virulence factors through LasR is required for enhancement of infection in the absence of Cftr. The zebrafish system provides a multitude of advantages for studying the pathogenesis of P. aeruginosa and for understanding the role that innate immune cells, such as neutrophils, play in the host response to acute bacterial infections commonly associated with cystic fibrosis.Cystic fibrosis (CF) is a multiorgan genetic disorder characterized by chronic pulmonary infections as well as gastrointestinal and reproductive abnormalities. In 1989, it was discovered that CF results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (25), which encodes a chloride ion channel present in most epithelial cells. Today, 80 to 95% of CF patients succumb to respiratory failure resulting from chronic lung infections that begin in early childhood and that are caused primarily by Pseudomonas aeruginosa (7, 32). Chronic infection with the bacterium leads to hyperinflammation characterized by the excessive recruitment of neutrophils to the airways and the subsequent release of oxidants and enzymes from activated neutrophils, which damages the lung tissue over time (32).Pseudomonas aeruginosa is a flagellated Gram-negative opportunistic pathogen of plants and animals and is found naturally in soil and water. As a nosocomial pathogen, it is the third most commonly isolated organism, leading primarily to urinary tract or wound infections in immunocompromised patients (17). Due to its production of alginate, the low permeability of its outer membrane and the presence of multidrug efflux pumps, P. aeruginosa exhibits a high degree of ...

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“…One further aspect to consider when reviewing the literature on neutrophil chemotaxis is the negative effect of acute bacterial infection. Indeed it has been shown that purified circulating neutrophils of clinically stable patients with CF migrate significantly faster than non-CF cells in response to IL-8 (Brennan et al 2001), whilst acutely infected infants (Kurland et al 1986) and also adults (Sener et al 1999) with CF showed a significant reduction in peripheral blood neutrophil chemotaxis and migration. Alginate of mucoid P. aeruginosa (Pedersen et al 1990) and exopolysaccharide from Burkholderia cenocepacia could be a factor in part responsible for these observations, as the latter has been shown to reduce neutrophil chemotactic responses (Bylund et al 2006).…”

Section: Neutrophil Chemotaxis and Migrationmentioning

confidence: 99%

The Cystic Fibrosis Neutrophil: A Specialized Yet Potentially Defective Cell

Hayes

Pohl

McElvaney

et al. 2011

Arch. Immunol. Ther. Exp.

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Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

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Neutrophil chemotaxis in acutely infected and clinically stable cystic fibrosis patients*

Abstract: The present study confirms that neutrophil chemotaxis and random migration are normal in clinically stable CF patients. The decreased CI in the acutely infected patients indicates the possible role of infection itself on neutrophil chemotaxis.

Cited by 9 publications

References 15 publications

Directed neutrophil migration to IL-8 is increased in cystic fibrosis: a study of the effect of erythromycin

Directed neutrophil migration to IL-8 is increased in cystic fibrosis: a study of the effect of erythromycin

Specific Resistance to Pseudomonas aeruginosa Infection in Zebrafish Is Mediated by the Cystic Fibrosis Transmembrane Conductance Regulator

The Cystic Fibrosis Neutrophil: A Specialized Yet Potentially Defective Cell

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