Lung protease/anti-protease network and modulation of mucus production and surfactant activity

García-Verdugo, Ignacio; Descamps, Delphyne; Chignard, Michel; Touqui, Lhousseine; Sallenave, Jean–Michel

doi:10.1016/j.biochi.2010.05.010

Cited by 36 publications

(19 citation statements)

References 187 publications

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“…The dual-protective role of human serum could explain why PVL-associated necrotizing diseases mainly develop under serum-free conditions, such as in pulmonary alveoli. Our in vivo experiments in murine lungs revealed that the alveolar surfactant, which also contains proteases inhibitors [32], did not confer sufficient protection against supernatants from PVL-treated neutrophils. PVL-producing strains are also frequently found in necrotizing skin infections, such as furunculosis and cabuncles [33], in which the onset of inflammation takes place under serum-free conditions within infected skin glands.…”

Section: Discussionmentioning

confidence: 99%

Combined Action of Influenza Virus and Staphylococcus aureus Panton–Valentine Leukocidin Provokes Severe Lung Epithelium Damage

Niemann¹,

Ehrhardt

Medina

et al. 2012

The Journal of Infectious Diseases

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Staphylococcus aureus necrotizing pneumonia is a life-threatening disease that is frequently preceded by influenza infection. The S. aureus toxin Panton–Valentine leukocidin (PVL) is most likely causative for necrotizing diseases, but the precise pathogenic mechanisms of PVL and a possible contribution of influenza virus remain to be elucidated. In this study, we present a model that explains how influenza virus and PVL act together to cause necrotizing pneumonia: an influenza infection activates the lung epithelium to produce chemoattractants for neutrophils. Upon superinfection with PVL-expressing S. aureus , the recruited neutrophils are rapidly killed by PVL, resulting in uncontrolled release of neutrophil proteases that damage the airway epithelium. The host counteracts this pathogen strategy by generating PVL-neutralizing antibodies and by neutralizing the released proteases via protease inhibitors present in the serum. These findings explain why necrotizing infections mainly develop in serum-free spaces (eg, pulmonary alveoli) and open options for new therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Combined Action of Influenza Virus and Staphylococcus aureus Panton–Valentine Leukocidin Provokes Severe Lung Epithelium Damage

Niemann¹,

Ehrhardt

Medina

et al. 2012

The Journal of Infectious Diseases

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“…Normally, NE plays an important role in the processing and release of cytokines (e.g. IL-6 [24]), modulation of immune cell activity and mucus secretion [25]. It is also important in the defence against gram negative bacteria including P. aeruginosa by cleaving bacterial cell surface structures, such as flagella.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of soluble and cellular inflammatory markers in nasal lavage obtained from Cystic Fibrosis patients during intravenous antibiotic treatment

et al. 2014

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BackgroundIn cystic fibrosis (CF) patients, the upper airways display the same ion channel defect as evident in the lungs, resulting in chronic inflammation and infection. Recognition of the sinonasal area as a site of first and persistent infection with pathogens, such as Pseudomonas aeruginosa, reinforces the “one-airway” hypothesis. Therefore, we assessed the effect of systemic antibiotics against pulmonary pathogens on sinonasal inflammation.MethodsNasal lavage fluid (NLF) from 17 CF patients was longitudinally collected prior to and during elective intravenous (i.v.) antibiotic treatment to reduce pathogen burden and resulting inflammation (median treatment time at time of analysis: 6 days). Samples were assessed microbiologically and cytologically. Cytokine and chemokine expression was measured by Cytometric Bead Array and ELISA (interleukin (IL)-1β, IL-6, IL-8, MPO, MMP9, RANTES and NE). Findings were compared with inflammatory markers from NLF obtained from 52 healthy controls.ResultsInitially, the total cell count of the NLF was significantly higher in CF patients than in controls. However after i.v. antibiotic treatment it decreased to a normal level. Compared with controls, detection frequencies and absolute concentrations of MPO, IL-8, IL-6 and IL-1β were also significantly higher in CF patients. The detection frequency of TNF was also higher. Furthermore, during i.v. therapy sinonasal concentrations of IL-6 decreased significantly (P = 0.0059), while RANTES and MMP9 levels decreased 10-fold and two-fold, respectively. PMN-Elastase, assessed for the first time in NFL, did not change during therapy.ConclusionsAnalysis of NLF inflammatory markers revealed considerable differences between controls and CF patients, with significant changes during systemic i.v. AB treatment within just 6 days. Thus, our data support further investigation into the collection of samples from the epithelial surface of the upper airways by nasal lavage as a potential diagnostic and research tool.

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“…Proteases released from neutrophils and epithelia perturb the protease-antiprotease balance (Voynow et al, 2008). This imbalance further contributes to the CF host defense defect by promoting increased secretion of mucins and the degradation of antimicrobials (Garcia-Verdugo et al, 2010). Some proteases, such as cathepsins, are activated by acidic pH and proteolytically cleave antimicrobials, including lactoferrin and lysozyme (Britigan et al, 1993), human β-defensins (Taggart et al, 2003), and SP-A (Lecaille et al, 2013), reducing their antimicrobial activity.…”

Section: Pathogenesismentioning

confidence: 99%

Effects of airway surface liquid pH on host defense in cystic fibrosis

Berkebile

McCray

2014

The International Journal of Biochemistry & Cell Biology

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Cystic fibrosis is a lethal genetic disorder characterized by viscous mucus and bacterial colonization of the airways. Airway surface liquid represents a first line of pulmonary defense. Studies in humans and animal models of cystic fibrosis indicate that the pH of airway surface liquid is reduced in the absence of cystic fibrosis transmembrane conductance regulator function. Many aspects of the innate host defense system of the airways are pH sensitive, including antimicrobial peptide/protein activity, the rheological properties of secreted mucins, mucociliary clearance, and the activity of proteases. This review will focus on how changes in airway surface liquid pH may contribute to the host defense defect in cystic fibrosis soon after birth. Understanding how changes in pH impact mucosal immunity may lead to new therapies that can modify the airway surface liquid environment, improve airway defenses, and alter the disease course.

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Lung protease/anti-protease network and modulation of mucus production and surfactant activity

Cited by 36 publications

References 187 publications

Combined Action of Influenza Virus and Staphylococcus aureus Panton–Valentine Leukocidin Provokes Severe Lung Epithelium Damage

Combined Action of Influenza Virus and Staphylococcus aureus Panton–Valentine Leukocidin Provokes Severe Lung Epithelium Damage

Dynamics of soluble and cellular inflammatory markers in nasal lavage obtained from Cystic Fibrosis patients during intravenous antibiotic treatment

Effects of airway surface liquid pH on host defense in cystic fibrosis

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