Exoproduct secretions of Pseudomonas aeruginosa strains influence severity of alveolar epithelial injury

1994 ◽  
Vol 267 (5) ◽  
pp. L551-L556 ◽  
Author(s):  
I. Kudoh ◽  
J. P. Wiener-Kronish ◽  
S. Hashimoto ◽  
J. F. Pittet ◽  
D. Frank
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lung Injury ◽  
Alveolar Epithelium ◽  
Infection Model ◽  
Epithelial Injury ◽  
Exoenzyme S ◽  
Alveolar Epithelial ◽  
Alveolar Epithelial Injury ◽  
Injury Control ◽  
Adp Ribosyltransferase

To determine whether exoenzyme S plays a role in alveolar epithelial injury, two parental strains of Pseudomonas aeruginosa, PAK and PA103, were tested that produced large quantities of exoenzyme S. Strains PAK and PA103 differ in the form of exoenzyme S they produce. Strain PAK produces a 53-kDa protein that does not possess ADP-ribosyltransferase activity and large quantities of a 49-kDa protein that expresses ADP-ribosyltransferase activity. Strain PA103 produces the 53-kDa protein and low amounts of exoenzyme S activity. A quantitative experimental protocol was used to measure the protein permeability of the alveolar epithelium and the dissemination of the bacteria to the pleural space and circulation. The results indicate that instillation of PAK and PA103 resulted in significant lung injury. Control experiments utilizing isogenic, exoenzyme S-deficient, regulatory mutants in the infection model reduced the lung injury and the dissemination of instilled bacteria. Taken together these results suggest that alveolar epithelial injury correlated with the production of the 53-kDa form of exoenzyme S or other coordinately regulated factors.

scholarly journals Surfactant Protein B Deficiency Induced High Surface Tension: Relationship between Alveolar Micromechanics, Alveolar Fluid Properties and Alveolar Epithelial Cell Injury

2019 ◽  
Vol 20 (17) ◽  
pp. 4243 ◽  
Author(s):  
Nina Rühl ◽  
Elena Lopez-Rodriguez ◽  
Karolin Albert ◽  
Bradford J Smith ◽  
Timothy E Weaver ◽  
...  
Keyword(s):  
Surface Tension ◽  
Lung Injury ◽  
High Surface ◽  
Surfactant Protein ◽  
Epithelial Injury ◽  
High Surface Tension ◽  
Alveolar Epithelial ◽  
Surfactant Protein B ◽  
Fluid Properties ◽  
Alveolar Epithelial Injury

High surface tension at the alveolar air-liquid interface is a typical feature of acute and chronic lung injury. However, the manner in which high surface tension contributes to lung injury is not well understood. This study investigated the relationship between abnormal alveolar micromechanics, alveolar epithelial injury, intra-alveolar fluid properties and remodeling in the conditional surfactant protein B (SP-B) knockout mouse model. Measurements of pulmonary mechanics, broncho-alveolar lavage fluid (BAL), and design-based stereology were performed as a function of time of SP-B deficiency. After one day of SP-B deficiency the volume of alveolar fluid V(alvfluid,par) as well as BAL protein and albumin levels were normal while the surface area of injured alveolar epithelium S(AEinjure,sep) was significantly increased. Alveoli and alveolar surface area could be recruited by increasing the air inflation pressure. Quasi-static pressure-volume loops were characterized by an increased hysteresis while the inspiratory capacity was reduced. After 3 days, an increase in V(alvfluid,par) as well as BAL protein and albumin levels were linked with a failure of both alveolar recruitment and airway pressure-dependent redistribution of alveolar fluid. Over time, V(alvfluid,par) increased exponentially with S(AEinjure,sep). In conclusion, high surface tension induces alveolar epithelial injury prior to edema formation. After passing a threshold, epithelial injury results in vascular leakage and exponential accumulation of alveolar fluid critically hampering alveolar recruitability.

Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits

1993 ◽  
Vol 75 (4) ◽  
pp. 1661-1669 ◽  
Author(s):  
J. P. Wiener-Kronish ◽  
T. Sakuma ◽  
I. Kudoh ◽  
J. F. Pittet ◽  
D. Frank ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Regulatory Gene ◽  
Pleural Empyema ◽  
Epithelial Barrier ◽  
Insertion Mutation ◽  
Epithelial Injury ◽  
Exoenzyme S ◽  
Alveolar Epithelial ◽  
Alveolar Epithelial Injury ◽  
Pleural Injury

We developed an experimental model of acute Pseudomonas aeruginosa pneumonia in anesthetized ventilated rabbits to determine whether bacterial-induced injury to the alveolar epithelium would occur and the effect of the injury on the pleural space. Dose-response studies established that 10(9) colony-forming units of P. aeruginosa (wild-type strain, PAO-1) were required to injure the epithelial barrier and to cause pleural empyema with exudative pleural effusions that contained both the instilled alveolar protein tracer and P. aeruginosa. We explored the mechanisms of P. aeruginosa-induced lung and pleural injury by using three isogenic bacterial strains to compare several extracellular virulence products. PAO-S21, which carries an insertion mutation in a regulatory gene that prevents the production of exoenzyme S, resulted in no lung or pleural injury. PAO-R1, which carries a deletion in a regulatory gene that controls the production of elastase and alkaline protease, caused the same degree of lung and pleural injury as PAO-1 did. Instillation of PLC-SRN, which has both structural genes encoding phospholipase C activity deleted, resulted in a moderate reduction in alveolar epithelial injury. Although other products may be involved, exoenzyme S and phospholipase C are important in mediating injury to the alveolar epithelial barrier in acute P. aeruginosa pneumonia in rabbits.

scholarly journals Structure–activity relationships for inhibitors of Pseudomonas aeruginosa exoenzyme S ADP-ribosyltransferase activity

2018 ◽  
Vol 143 ◽  
pp. 568-576 ◽  
Author(s):  
Michael Saleeb ◽  
Charlotta Sundin ◽  
Öznur Aglar ◽  
Ana Filipa Pinto ◽  
Mahsa Ebrahimi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Exoenzyme S ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Adp Ribosyltransferase

scholarly journals Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model

1999 ◽  
Vol 43 (10) ◽  
pp. 2389-2394 ◽  
Author(s):  
Erika J. Ernst ◽  
Satoru Hashimoto ◽  
Joseph Guglielmo ◽  
Teiji Sawa ◽  
Jean-Francois Pittet ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Rat Model ◽  
In Vivo Model ◽  
Antibiotic Administration ◽  
Lung Water ◽  
Alveolar Epithelial ◽  
The Right

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

scholarly journals The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia

2020 ◽  
Vol 319 (2) ◽  
pp. L218-L227 ◽  
Author(s):  
James T. Ross ◽  
Nicolas Nesseler ◽  
Aleksandra Leligdowicz ◽  
Rachel L. Zemans ◽  
Rahul Y. Mahida ◽  
...  
Keyword(s):  
Human Lung ◽  
Ex Vivo ◽  
Alveolar Epithelium ◽  
Lung Model ◽  
High Dose ◽  
Alveolar Epithelial ◽  
Low Protein ◽  
Alveolar Epithelial Injury ◽  
High Doses ◽  
Protein Permeability

Few patients with bacteremia from a nonpulmonary source develop acute respiratory distress syndrome (ARDS). However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding Streptococcus pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.

Detection of alveolar epithelial injury by Tc-99m DTPA radioaerosol inhalation lung scan in rheumatoid arthritis patients

2005 ◽  
Vol 19 (6) ◽  
pp. 455-460 ◽  
Author(s):  
Berna Okudan ◽  
Mehmet Şahİn ◽  
Feride Meltem Özbek ◽  
Ali Ümit Keskİn ◽  
Erkan Cüre
Keyword(s):  
Rheumatoid Arthritis ◽  
Epithelial Injury ◽  
Alveolar Epithelial ◽  
Lung Scan ◽  
Alveolar Epithelial Injury

Reticulocalbin 3 deficiency in alveolar epithelium attenuated LPS-induced ALI via NF-κB signaling

2021 ◽  
Vol 320 (4) ◽  
pp. L627-L639
Author(s):  
Xiaoqian Shi ◽  
Xiaojie An ◽  
Liu Yang ◽  
Zhipeng Wu ◽  
Danni Zan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Secretory Pathway ◽  
Alveolar Epithelium ◽  
Repair Process ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury (ALI) secondary to an excessive alveolar inflammatory response. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein in the secretory pathway. We previously reported the indispensable role of Rcn3 in type II alveolar epithelial cells (AECIIs) during lung development and the lung injury repair process. In the present study, we further observed a marked induction of Rcn3 in the alveolar epithelium during LPS-induced ALI. In vitro alveolar epithelial (MLE-12) cells consistently exhibited a significant induction of Rcn3 accompanied with NF-κB activation in response to LPS exposure. We examined the role of Rcn3 in the alveolar inflammatory response by using mice with a selective deletion of Rcn3 in alveolar epithelial cells upon doxycycline administration. The Rcn3 deficiency significantly blunted the ALI and alveolar inflammation induced by intratracheal LPS instillation but not that induced by an intraperitoneal LPS injection (secondary insult); the alleviated ALI was accompanied by decreases in NF-κB activation and NLRP3 levels but not in GRP78 and cleaved caspase-3 levels. The studies conducted in MLE-12 cells consistently showed that Rcn3 knockdown blunted the activations of NF-κB signaling and NLRP3-dependent inflammasome upon LPS exposure. Collectively, these findings suggest a novel role for Rcn3 in regulating the alveolar inflammatory response to pulmonary infection via the NF-κB/NLRP3/inflammasome axis and shed additional light on the mechanism of ARDS/ALI.

scholarly journals Comparison of the exoS Gene and Protein Expression in Soil and Clinical Isolates of Pseudomonas aeruginosa

2001 ◽  
Vol 69 (4) ◽  
pp. 2198-2210 ◽  
Author(s):  
Michael W. Ferguson ◽  
Jill A. Maxwell ◽  
Timothy S. Vincent ◽  
Jack da Silva ◽  
Joan C. Olson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Structural Gene ◽  
Gene Sequence ◽  
Specific Activity ◽  
Clinical Isolates ◽  
Secretory Process ◽  
Sequence Comparisons ◽  
Exoenzyme S ◽  
Gene And Protein Expression ◽  
Adp Ribosyltransferase

ABSTRACT Exoenzyme S (ExoS) is translocated into eukaryotic cells by the type III secretory process and has been hypothesized to function in conjunction with other virulence factors in the pathogenesis ofPseudomonas aeruginosa. To gain further understanding of how ExoS might contribute to P. aeruginosa survival and virulence, ExoS expression and the structural gene sequence were determined in P. aeruginosa soil isolates and compared with ExoS of clinical isolates. Significantly higher levels of ExoS ADP-ribosyltransferase (ADPRT) activity were detected in culture supernatants of soil isolates compared to those of clinical isolates. The higher levels of ADPRT activity of soil isolates reflected both the increased production of ExoS and the production of ExoS having a higher specific activity. ExoS structural gene sequence comparisons found the gene to be highly conserved among soil and clinical isolates, with the greatest number of nonsynonymous substitutions occurring within the region of ExoS encoding GAP function. The lack of amino acid changes in the ADPRT region in association with a higher specific activity implies that other factors produced by P. aeruginosa or residues outside the ADPRT region are affecting ExoS ADPRT activity. The data are consistent with ExoS being integral to P. aeruginosa survival in the soil and suggest that, in the transition of P. aeruginosa from the soil to certain clinical settings, the loss of ExoS expression is favored.

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