Coordinated clearance of periciliary liquid and mucus from airway surfaces.

Matsui, Hirotoshi; Randell, Scott H.; Peretti, Steven W.; Davis, C. William; Boucher, Richard C.

doi:10.1172/jci2687

Cited by 347 publications

(352 citation statements)

References 31 publications

Supporting

Mentioning

326

Contrasting

Unclassified

Order By: Relevance

“…Human tracheo-bronchial epithelial cells (CF and normal) were isolated and cultured under air-liquid conditions as previously described (38). Mucus harvested from Ϸ200 concurrent cultures was pooled and stored at 4°C.…”

Section: Methods Preparation Of Concentrated Mucusmentioning

confidence: 99%

A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms

Matsui¹,

Wagner

Hill³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

217

228

View full text Add to dashboard Cite

A vexing problem in cystic fibrosis (CF) pathogenesis has been to explain the high prevalence of Pseudomonas aeruginosa biofilms in CF airways. We speculated that airway surface liquid (ASL) hyperabsorption generates a concentrated airway mucus that interacts with P. aeruginosa to promote biofilms. To model CF vs. normal airway infections, normal (2.5% solids) and CF-like concentrated (8% solids) mucus were prepared, placed in flat chambers, and infected with an Ϸ5 ؋ 10 3 strain PAO1 P. aeruginosa. Although bacteria grew to 10 10 cfu/ml in both mucus concentrations, macrocolony formation was detected only in the CF-like (8% solids) mucus. Biophysical and functional measurements revealed that concentrated mucus exhibited properties that restrict bacterial motility and small molecule diffusion, resulting in high local bacterial densities with high autoinducer concentrations. These properties also rendered secondary forms of antimicrobial defense, e.g., lactoferrin, ineffective in preventing biofilm formation in a CF-like mucus environment. These data link airway surface liquid hyperabsorption to the high incidence of P. aeruginosa biofilms in CF via changes in the hydration-dependent physical-chemical properties of mucus and suggest that the thickened mucus gel model will be useful to develop therapies of P. aeruginosa biofilms in CF airways.mucus ͉ rheology C ystic fibrosis (CF) lung disease reflects the chronic bacterial infection of intrapulmonary airways with Pseudomonas aeruginosa biofilms (1, 2). P. aeruginosa biofilms have mostly been studied in flow chambers (3-7) that are good models for the biofilms that form on venous or urethral catheters under conditions of high flow rates and relatively high oxygen tensions. However, biofilms in CF airways form in thickened (concentrated) mucus gels that are relatively hypoxic and adherent to airway surfaces (see Fig. 1A) (8, 9). Recently, Sriramulu et al. (10) investigated the role autoregulators and amino acids play in the tightness of biofilm formation in a mucus stimulant of constant hydration. For the present study, we designed a culture system to investigate whether dehydration of the CF mucus environment may predispose to P. aeruginosa biofilm formation.A key aspect of the model was the selection of mucus concentrations that mimic normal and CF mucus. Although measurements of mucus concentration, i.e., the percentage of solids content, from CF subjects before infection have not been reported, estimates from cell cultures (11) and sputum (12-18) suggest that CF mucus is at least three or four times more concentrated than normal. Therefore, mucus was obtained from well differentiated human airway cultures and was isotonically concentrated (1) to produce mucus of normal (2.5% solids wt/wt) and CF-like (8%) concentrations (Fig. 1B). Aliquots of each were deposited in (i) an open chamber to model a mucus plaque adherent to CF airway surfaces with a residual lumen allowing airflow and (ii) a closed chamber to mimic a mucus plug occluding a CF airway (Fig. 1 A). P....

show abstract

Section: Methods Preparation Of Concentrated Mucusmentioning

confidence: 99%

A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms

Matsui¹,

Wagner

Hill³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

217

228

View full text Add to dashboard Cite

show abstract

“…Further studies in human tracheobronchial epithelial cultures (Matsui et al, 1998) recently demonstrated that the entire periciliary fluid is transported at approximately the same rate as mucus (about 40 mm/s), and that the removal of the mucous layer reduced periciliary fluid transport by more than 80%. The cephalad movement of periciliary liquid along airway epithelial surfaces makes this mucus-driven transport an important component of salt and water physiology in the lungs.…”

Section: Mucociliary Clearancementioning

confidence: 99%

Mild dehydration: a risk factor of broncho-pulmonary disorders?

Kalhoff¹

2003

Eur J Clin Nutr

View full text Add to dashboard Cite

Several expert committees recommend a high fluid intake in patients with chronic bronchitis and asthma. Is there a relationship between fluid intake or hydration status and broncho-pulmonary disorders like bronchitis and asthma? First, basic physiologic mechanisms like regulation of lung fluid balance and water transport at pulmonary surfaces were analyzed, in order to characterize the role of local hydration status in lung and airways. Second, making use of the computerbased literature searches (PubMed), evidence for a role of hydration status in complex physiological and pathophysiological conditions of lungs and airways like perinatal lung adaptation (PLA) (in prematures), mucociliary clearance(MC) and asthma was categorized. The movement of fluid between the airspaces, interstitium, and vascular compartments in the lungs plays an important physiological role in the maintenance of hydration and protection of the lung epithelium and significantly contributes to a proper airway clearance. PLA is characterized by a rapid change from fluid secretion to fluid absorption in the distal respiratory tract, with the literature data confirming a critical role of the epithelial sodium channel. Only few studies have investigated the effect of different fluid input regimens on PLA in prematures. MC relies on the interaction between epithelial water fluxes, mucus secretions, and ciliary activity. Whereas animal data show that drying of the airway epithelium decreases MC, few clinical studies investigating the effect of local or systemic hydration on MC have led to ambiguous results. Asthma (A) is characterized by chronic airway inflammation and episodic airway obstruction. Data in animals and humans indicate an association between exercise-induced-A and conditioning (humidity and heat exchange) of inspired air. However, epidemiological studies (children and adults), investigating the role of fluid (and salt) input in the etiology of the disease as well as studies analyzing different markers of hydration status during asthmatic attacks have so far led to conflicting results. Some expert groups recommend sufficient hydration as a complementary A-therapy. Analysis of basic physiological mechanisms in lungs and airways clearly demonstrates a critical role for water transport and local hydration status. In broncho-pulmonary diseases, however, analysis of the complex pathophysiological mechanisms is difficult. Thus, we still need more studies to confirm or refute mild dehydration or hypohydration as a risk factor of broncho-pulmonary disorders.

show abstract

“…Thickened secretions caused by improper regulation of airway surface liquid contribute to the accumulation of mucus in the airway and defective mucociliary clearance (2). Retained mucus plugs provide a niche for bacterial colonization and persistence.…”

mentioning

confidence: 99%

Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis

Harris

Groote

Sagel³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

351

342

View full text Add to dashboard Cite

Culture of bronchoalveolar lavage fluid (BALF) is the gold standard for detection of pathogens in the lower airways in cystic fibrosis (CF). However, current culture results do not explain all clinical observations in CF, including negative culture results during pulmonary exacerbation and inflammation in the absence of pathogens. We hypothesize that organisms not routinely identified by culture occur in the CF airway and may contribute to disease. To test this hypothesis we used a culture-independent molecular approach, based on use of rRNA sequence analysis, to assess the bacterial composition of BALF from children with CF and disease controls (DC). Specimens from 42 subjects (28 CF) were examined, and Ϸ6,600 total clones were screened to identify 121 species of bacteria. In general, a single rRNA type dominated clone libraries from CF specimens, but not DC. Thirteen CF subjects contained bacteria that are not routinely assessed by culture. In four CF subjects, candidate pathogens were identified and include the anaerobe Prevotella denticola, a Lysobacter sp., and members of the Rickettsiales. The presumptive pathogens Tropheryma whipplei and Granulicatella elegans were identified in cases from the DC group. The presence of unexpected bacteria in CF may explain inflammation without documented pathogens and consequent failure to respond to standard treatment. These results show that molecular techniques provide a broader perspective on airway bacteria than do routine clinical cultures and thus can identify targets for further clinical evaluation. pulmonary microbiology ͉ ribosomal RNA C ystic fibrosis (CF), the most common autosomal lethal disease in Caucasians, is caused by mutation in the CF transmembrane conductance regulator gene, which results in a generalized exocrinopathy (1). Thickened secretions caused by improper regulation of airway surface liquid contribute to the accumulation of mucus in the airway and defective mucociliary clearance (2). Retained mucus plugs provide a niche for bacterial colonization and persistence. Most morbidity and mortality associated with CF is attributed to microbial infections in the airway and the persistent inflammatory response (3).A small number of pathogens are recognized traditionally in CF airway disease. These include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and the Burkholderia cepacia complex (4-7). Other bacteria, including Stenotrophomonas maltophilia and Achromobacter xylosoxidans, also are associated with CF, but there is controversy as to their roles as pathogens (8)(9)(10). This view of bacteria associated with CF is based on culture, however, which may not recover or identify all bacteria present in a specimen. Although known pathogens clearly are important in airway disease, a more comprehensive picture of the bacterial community in the CF airway potentially could lead to improved insight about the disease and thus better treatment. For instance, ''normal'' microbiota that are commonly present, but not considered pathogenic, ...

show abstract

Coordinated clearance of periciliary liquid and mucus from airway surfaces.

Cited by 347 publications

References 31 publications

A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms

A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms

Mild dehydration: a risk factor of broncho-pulmonary disorders?

Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis

Contact Info

Product

Resources

About