Lactate in cystic fibrosis sputum

Bensel, Tobias; Stotz, Martin; Borneff-Lipp, M.; Wollschläger, B; Wienke, Andreas; Taccetti, Giovanni; Campana, S.; Meyer, Keith C.; Jensen, Peter Østrup; Lechner, Ute; Ulrich, Martina; Döring, Gerd; Worlitzsch, Dieter

doi:10.1016/j.jcf.2010.09.004

Cited by 50 publications

(57 citation statements)

References 37 publications

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“…through fermentation [48]. Lactate has been detected in the CF sputum at a mean concentration of 3 mM, and higher concentrations have been correlated with lower lung function [49]. Because LDHs enable cells to use lactate as an energy source for growth and reproduction, they are considered as virulence factors.…”

Section: Resultsmentioning

confidence: 99%

Mechanistic Model of Rothia mucilaginosa Adaptation toward Persistence in the CF Lung, Based on a Genome Reconstructed from Metagenomic Data

et al. 2013

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The impaired mucociliary clearance in individuals with Cystic Fibrosis (CF) enables opportunistic pathogens to colonize CF lungs. Here we show that Rothia mucilaginosa is a common CF opportunist that was present in 83% of our patient cohort, almost as prevalent as Pseudomonas aeruginosa (89%). Sequencing of lung microbial metagenomes identified unique R. mucilaginosa strains in each patient, presumably due to evolution within the lung. The de novo assembly of a near-complete R. mucilaginosa (CF1E) genome illuminated a number of potential physiological adaptations to the CF lung, including antibiotic resistance, utilization of extracellular lactate, and modification of the type I restriction-modification system. Metabolic characteristics predicted from the metagenomes suggested R. mucilaginosa have adapted to live within the microaerophilic surface of the mucus layer in CF lungs. The results also highlight the remarkable evolutionary and ecological similarities of many CF pathogens; further examination of these similarities has the potential to guide patient care and treatment.

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Section: Resultsmentioning

confidence: 99%

Mechanistic Model of Rothia mucilaginosa Adaptation toward Persistence in the CF Lung, Based on a Genome Reconstructed from Metagenomic Data

et al. 2013

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“…The lactate so produced is also a chemoattractant for immune cells (Lardner, ). In addition, formalin injection causes an immense infiltration of neutrophils, which are an authentic source of lactate (Simchowitz and Textor, ; Bensel et al, ), at the site of localized inflammation because of the altered mitochondrial metabolism (Jha et al, ). Moreover, we previously reported that lactate levels are substantially increased at the local inflammation site following intraplantar inflammatory challenge (Jha et al, ).…”

Section: Discussionmentioning

confidence: 99%

Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain

Jha

Rahman

Park

et al. 2016

J of Neuroscience Research

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Pyruvate dehydrogenase (PDH) kinases (PDKs) 1-4, expressed in peripheral and central tissues, regulate the activity of the PDH complex (PDC). The PDC is an important mitochondrial gatekeeping enzyme that controls cellular metabolism. The role of PDKs in diverse neurological disorders, including neurometabolic aberrations and neurodegeneration, has been described. Implications for a role of PDKs in inflammation and neurometabolic coupling led us to investigate the effect of genetic ablation of PDK2/4 on nociception in a mouse model of acute inflammatory pain. Deficiency in Pdk2 and/or Pdk4 in mice led to attenuation of formalin-induced nociceptive behaviors (flinching, licking, biting, or lifting of the injected paw). Likewise, the pharmacological inhibition of PDKs substantially diminished the nociceptive responses in the second phase of the formalin test. Furthermore, formalin-provoked paw edema formation and mechanical and thermal hypersensitivities were significantly reduced in Pdk2/4-deficient mice. Formalin-driven neutrophil recruitment at the site of inflammation, spinal glial activation, and neuronal sensitization were substantially lessened in the second or late phase of the formalin test in Pdk2/4-deficient animals. Overall, our results suggest that PDK2/4 can be a potential target for the development of pharmacotherapy for the treatment of acute inflammatory pain. © 2016 Wiley Periodicals, Inc.

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“…Further study will be necessary to confirm the extent to which lactate is taken up and utilized by ATII cells when glucose is also present; however, this work establishes that ATII cell glucose metabolism is responsive to extracellular lactate. This may have considerable implications for ATII cell function in disease, since plasma lactate can exceed 20 mM in extreme cases of hypoxia or hypotension (25), and pulmonary tissue concentrations increase more than twofold from normal levels in idiopathic pulmonary fibrosis (IPF) patient parenchymal tissue (22) and possibly in cystic fibrosis, based on elevated lactate measured in patient sputum samples (1).…”

Section: Discussionmentioning

confidence: 99%

Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells

Lottes

Newton

Spyropoulos

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lottes RG, Newton DA, Spyropoulos DD, Baatz JE. Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells. Am J Physiol Lung Cell Mol Physiol 308: L953-L961, 2015. First published March 6, 2015 doi:10.1152/ajplung.00335.2014.-Because of the many energy-demanding functions they perform and their physical location in the lung, alveolar epithelial type II (ATII) cells have a rapid cellular metabolism and the potential to influence substrate availability and bioenergetics both locally in the lung and throughout the body. A thorough understanding of ATII cell metabolic function in the healthy lung is necessary for determining how metabolic changes may contribute to pulmonary disease pathogenesis; however, lung metabolism is poorly understood at the cellular level. Here, we examine lactate utilization by primary ATII cells and the ATII model cell line, MLE-15, and link lactate consumption directly to mitochondrial ATP generation. ATII cells cultured in lactate undergo mitochondrial respiration at near-maximal levels, two times the rates of those grown in glucose, and oxygen consumption under these conditions is directly linked to mitochondrial ATP generation. When both lactate and glucose are available as metabolic substrate, the presence of lactate alters glucose metabolism in ATII to favor reduced glycolytic function in a dose-dependent manner, suggesting that lactate is used in addition to glucose when both substrates are available. Lactate use by ATII mitochondria is dependent on monocarboxylate transporter (MCT)-mediated import, and ATII cells express MCT1, the isoform that mediates lactate import by cells in other lactate-consuming tissues. The balance of lactate production and consumption may play an important role in the maintenance of healthy lung homeostasis, whereas disruption of lactate consumption by factors that impair mitochondrial metabolism, such as hypoxia, may contribute to lactic acid build-up in disease. mitochondrial function; metabolism; hypoxia FROM A METABOLIC perspective, the lung is a unique physiological environment. The cells that compose the alveolar epithelium form the barrier between external air and the pulmonary vasculature in the best-oxygenated environment in the body. While terminally differentiated alveolar epithelial type I (ATI) cells form the passive surface across which gas exchange occurs, alveolar epithelial type II (ATII) cells perform a variety of energetically costly functions, including pulmonary surfactant production (16), fluid transport and homeostasis (27), immune functions (6, 23), and progenitor roles for self-renewal and transdifferentiation to repopulate ATI cells (5, 19). Additionally, the lung is the only organ apart from the heart itself that receives the entire cardiac output upon every passage through the body. Metabolic activity in the cells that compose the alveolar epithelium could potentially influence substrate availability, energy production, and redox balance locally and throughout the whole body (20, 32). While the lung...

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Lactate in cystic fibrosis sputum

Abstract: Successful antibiotic therapy is reflected by a decrease in lactate concentrations. Neutrophils are the most likely source for lactate in sputum of CF patients. Therefore lactate may be used to monitor responses to antibiotic therapy as an adjunct to lung function measurements.

Cited by 50 publications

References 37 publications

Mechanistic Model of Rothia mucilaginosa Adaptation toward Persistence in the CF Lung, Based on a Genome Reconstructed from Metagenomic Data

Mechanistic Model of Rothia mucilaginosa Adaptation toward Persistence in the CF Lung, Based on a Genome Reconstructed from Metagenomic Data

Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain

Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells

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