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Int. J. Mol. Sci. 2018, 19(1), 207;

Synthesized Heparan Sulfate Competitors Attenuate Pseudomonas aeruginosa Lung Infection

Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano 20132, Italy
Vita-Salute San Raffaele University, Milano 20132, Italy
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)
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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

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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).

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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.

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