Next Article in Journal
In Silico Analysis of the Association Relationship between Neuroprotection and Flavors of Traditional Chinese Medicine Based on the mGluRs
Next Article in Special Issue
Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke
Previous Article in Journal
Aeginetia indica Decoction Inhibits Hepatitis C Virus Life Cycle
Previous Article in Special Issue
Fungi in Bronchiectasis: A Concise Review
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(1), 207; doi:10.3390/ijms19010207

Synthesized Heparan Sulfate Competitors Attenuate Pseudomonas aeruginosa Lung Infection

1
Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano 20132, Italy
2
Vita-Salute San Raffaele University, Milano 20132, Italy
3
Istituto di Ricerche Chimiche e Biochimiche “G. Ronzoni”, Milano 20133, Italy
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 4 January 2018 / Accepted: 5 January 2018 / Published: 9 January 2018
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections)
View Full-Text   |   Download PDF [1628 KB, uploaded 9 January 2018]   |  

Abstract

Several chronic respiratory diseases are characterized by recurrent and/or persistent infections, chronic inflammatory responses and tissue remodeling, including increased levels of glycosaminoglycans which are known structural components of the airways. Among glycosaminoglycans, heparan sulfate (HS) has been suggested to contribute to excessive inflammatory responses. Here, we aim at (i) investigating whether long-term infection by Pseudomonas aeruginosa, one of the most worrisome threat in chronic respiratory diseases, may impact HS levels, and (ii) exploring HS competitors as potential anti-inflammatory drugs during P. aeruginosa pneumonia. P. aeruginosa clinical strains and ad-hoc synthesized HS competitors were used in vitro and in murine models of lung infection. During long-term chronic P. aeruginosa colonization, infected mice showed higher heparin/HS levels, evaluated by high performance liquid chromatography-mass spectrometry after selective enzymatic digestion, compared to uninfected mice. Among HS competitors, an N-acetyl heparin and a glycol-split heparin dampened leukocyte recruitment and cytokine/chemokine production induced by acute and chronic P. aeruginosa pneumonia in mice. Furthermore, treatment with HS competitors reduced bacterial burden during chronic murine lung infection. In vitro, P. aeruginosa biofilm formation decreased upon treatment with HS competitors. Overall, these findings support further evaluation of HS competitors as a novel therapy to counteract inflammation and infection during P. aeruginosa pneumonia. View Full-Text
Keywords: Pseudomonas aeruginosa infections; glycosaminoglycans; anti-inflammatory drugs; mouse models; chronic respiratory diseases Pseudomonas aeruginosa infections; glycosaminoglycans; anti-inflammatory drugs; mouse models; chronic respiratory diseases
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lorè, N.I.; Veraldi, N.; Riva, C.; Sipione, B.; Spagnuolo, L.; De Fino, I.; Melessike, M.; Calzi, E.; Bragonzi, A.; Naggi, A.; Cigana, C. Synthesized Heparan Sulfate Competitors Attenuate Pseudomonas aeruginosa Lung Infection. Int. J. Mol. Sci. 2018, 19, 207.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top