Effect of Recombinant Human DNase on α1-Proteinase Inhibitor Function: An Experimental Approach to the Combined Clinical Use of rhDNase and α1-PI in CF Patients

Hansen, Georg Nørgaard; Hoffjan, Sabine; Mosler, Katharina; Schuster, Antje

doi:10.1007/s004080000060

Cited by 9 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The primary targets for the liberated elastase are NET-associated histones and their subsequent enzymatic digest improves eDNA fragmentation [9]. However, the question remains whether the released active elastase should be controlled by addition of protease inhibitors [8,37] or whether alternative therapies that reduce the levels of NETosis should be devised.…”

Section: Discussionmentioning

confidence: 99%

Cystic Fibrosis Sputum DNA Has NETosis Characteristics and Neutrophil Extracellular Trap Release Is Regulated by Macrophage Migration-Inhibitory Factor

Dwyer

Shan²,

D'Ortona³

et al. 2014

J Innate Immun

176

165

View full text Add to dashboard Cite

Neutrophils are the main proinflammatory cell type in chronically infected lungs of cystic fibrosis (CF) patients; however, they fail to effectively clear the colonizing pathogens. Here, we investigated the molecular composition of non-mucoid and mucoid Pseudomonas aeruginosa-induced neutrophil extracellular traps (NETs) in vitro and compared them to the DNA-protein complexes present in the CF sputum. The protein composition of P. aeruginosa-induced NET fragments revealed that irrespective of the inducing stimuli, NET fragments were decorated with a conserved set of proteins. The DNA-protein complexes derived from CF sputum were consistent with NETosis and shared a similar protein signature, suggesting that the majority of the extracellular DNA was NET derived. The ability of polymorphonuclear leukocytes to produce NETs in response to P. aeruginosa was driven by macrophage migration-inhibitory factor (MIF) by promoting mitogen-activated protein kinase. Analysis of 132 CF patient samples revealed that elevated MIF protein levels correlated with poorer lung function. We suggest that targeting MIF by small molecular inhibitors might reduce the presence of extracellular DNA and serve as an adjunct to the use of antimicrobial drugs that could ultimately reduce bacterial fitness in the lungs during the later stages of CF disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Cystic Fibrosis Sputum DNA Has NETosis Characteristics and Neutrophil Extracellular Trap Release Is Regulated by Macrophage Migration-Inhibitory Factor

Dwyer

Shan²,

D'Ortona³

et al. 2014

J Innate Immun

176

165

View full text Add to dashboard Cite

show abstract

“…On the other hand, it has been proposed that rhDNase can promote mixing of bacteria, antimicrobial agent and sputum [184] and improve gene transfer [185 -187] by improving penetration through sputum. It has been suggested that rhDNase may liberate cationic mediators such as neutrophil elastase bound to DNA in the airways [188,189] and hypertonic saline may potentiate neutrophilic inflammation. However, this hypothesis has not been confirmed in clinical studies [190 -192].…”

Section: Anti-inflammatory Treatment Strategiesmentioning

confidence: 99%

Early intervention and prevention of lung disease in cystic fibrosis: a European consensus

Döring

Høiby

2004

Journal of Cystic Fibrosis

283

254

View full text Add to dashboard Cite

In patients with cystic fibrosis (CF), early intervention and prevention of lung disease is of paramount importance. Principles to achieve this aim include early diagnosis of CF, regular monitoring of the clinical status, various hygienic measures to prevent infection and cross-infection, early use of antibiotic courses in patients with recurrent or continuous bacterial colonisation and appropriate use of chest physiotherapy.

show abstract

“…1 Recombinant human DNase (rhDNase) degrades highly viscosic DNA and was shown to be efficient in patients with cystic fibrosis (CF). 2,3 The use of rhDNase for the treatment of atelectasis in patients in the neonatal intensive care unit is a new concept, intended to liquefy the mucus when conventional therapies fail. 4 We present our experience with rhDNase use in a premature infant with recurrent atelectasis.…”

mentioning

confidence: 99%

Use of recombinant human DNase in a premature infant with recurrent atelectasis

Küpeli¹,

Tekşam²,

Yurdakök³

2003

Pediatr Int

View full text Add to dashboard Cite

Key wordsatelectasis, premature neonate, rhDNase.Presence of mucus-plugging and abundance of thickened pulmonary secretions in the neonatal period are risk factors for pulmonary infections and prolonged artificial ventilation. The viscoelastic properties of airway secretions was known to be largely due to the presence of highly polymerized DNA. 1 Recombinant human DNase (rhDNase) degrades highly viscosic DNA and was shown to be efficient in patients with cystic fibrosis (CF). 2,3 The use of rhDNase for the treatment of atelectasis in patients in the neonatal intensive care unit is a new concept, intended to liquefy the mucus when conventional therapies fail. 4 We present our experience with rhDNase use in a premature infant with recurrent atelectasis. CaseA female infant of 29 weeks, 1 day gestation and a birth weight of 1040 g was delivered to a 30-year-old mother by cesarean section, because of intrauterine growth retardation, non-reactive non-stress test and breech presentation. Six days before delivery, the mother had spontaneous rupture of membranes and received erythromycin. The mother was a hepatitis B surface antigen (HBsAg) carrier and there was no consanguinity between the parents. The Apgar scores were 5, 7 and 9 at 1, 5 and 10 m. The placenta and the umbilical cord were normal in appearance, no pathological examination was performed. The patient's general condition was moderate-togood after birth: skin color was pink, activity was good, body temperature was 36.1 ° C, heart rate was 132/minute, respiratory rate was 48/minute, and blood pressure was 50/22 mmHg. In the complete blood count (CBC) the following were found: hemoglobin 16.3 g/dL, hematocrit 48.4%, white blood cell count 7.000/ µ l, mean corpuscular volume (MCV) 107.9 fl, red cell distribution width (RDW) 14.7, platelets 205.000/ µ l. C-reactive protein (CRP) was <0.01 mg/dL. Blood sugars were found to be 89 and 106 mg/dL at 2 and 6 h after birth, respectively. Oxygen saturation measured with pulse oxymetry was found to be 94%. No microorganisms were cultured in blood or urine samples taken on the patient's first day of life. No infiltration was found on chest X-ray and her cranial ultrosonographic examination was normal. The patient was given both hepatitis B immunoglobulin and hepatitis B vaccine. She was started on ampicillin and netilmycin because of the mother's history of preterm rupture of the membranes. The chest X-rays of the patient were not compliant with respiratory distress syndrome (RDS). On the third day of life, the infant had been apneic and had an increase in her oxygen requirement with pneumonic infiltration visible on chest X-ray. The patient was not hypothermic nor was she hyperthermic. There was no electrolyte imbalance or acidosis in her biochemistry and blood gas examination. She was not anemic. She was not RDS but there was an infiltration on chest X-ray. To treat apnea, first nasal continuous positive airway pressure (CPAP) (day 3), then nasal synchronized intermittent mandatory ventilation (SIMV) (day 4) was applied...

show abstract

Effect of Recombinant Human DNase on α1-Proteinase Inhibitor Function: An Experimental Approach to the Combined Clinical Use of rhDNase and α1-PI in CF Patients

Cited by 9 publications

References 0 publications

Cystic Fibrosis Sputum DNA Has NETosis Characteristics and Neutrophil Extracellular Trap Release Is Regulated by Macrophage Migration-Inhibitory Factor

Cystic Fibrosis Sputum DNA Has NETosis Characteristics and Neutrophil Extracellular Trap Release Is Regulated by Macrophage Migration-Inhibitory Factor

Early intervention and prevention of lung disease in cystic fibrosis: a European consensus

Use of recombinant human DNase in a premature infant with recurrent atelectasis

Contact Info

Product

Resources

About