Partially-desulfated heparin improves survival in Pseudomonas pneumonia by enhancing bacterial clearance and ameliorating lung injury

Lokesh Sharma, Jiao Wu, Vivek Patel, Ravikumar Sitapara, Narayanam V. Rao, Thomas P. Kennedy, Lin L. Mantell

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nosocomial pneumonia (NP, or hospital-acquired pneumonia) is associated with infections originating from hospital-borne pathogens. Persistent microbial presence and acute lung injury are common features of these infections, contributing to the high mortality rates and excessive financial burden for these patients. Pseudomonas aeruginosa (PA), a gram-negative opportunistic pathogen, is one of the prominent pathogens associated with NP. PA pneumonia is characterized by excessive secretion of inflammatory cytokines, neutrophil infiltration, and subsequent lung damage. The persistent presence of PA along with overwhelming inflammatory response is suggestive of impairment in innate immunity. High mobility group box 1 (HMGB1), a recently discovered potent pro-inflammatory cytokine, plays an important role in PA lung infections by compromising innate immunity via impairing phagocyte function through toll-like receptors (TLR) TLR2 and TLR4. ODSH (2-O, 3-O-desulfated heparin), a heparin derivative with significant anti-inflammatory properties but minimal anti-coagulatory effects, has been shown to reduce neutrophilic lung injury in the absence of active microbial infections. This study examined the effects of ODSH on PA pneumonia. This study demonstrates that ODSH not only reduced PA-induced lung injury, but also significantly increased bacterial clearance. The ameliorated lung injury, together with the increased bacterial clearance, resulted in marked improvement in the survival of these animals. The resulting attenuation in lung injury and improvement in bacterial clearance were associated with decreased levels of airway HMGB1. Furthermore, binding of HMGB1 to its receptors TLR2 and TLR4 was blunted in the presence of ODSH. These data suggest that ODSH provides a potential novel approach in the adjunctive treatment of PA pneumonia.

Original languageEnglish (US)
Pages (from-to)260-267
Number of pages8
JournalJournal of Immunotoxicology
Volume11
Issue number3
DOIs
StatePublished - Jan 1 2014

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Bacterial Pneumonia
Lung Injury
Pseudomonas
Pseudomonas aeruginosa
Heparin
Pathogens
Pneumonia
Survival
Bridge clearances
Innate Immunity
Cytokines
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
Infection
Infiltration
Lung
Neutrophil Infiltration
Acute Lung Injury
Animals

All Science Journal Classification (ASJC) codes

  • Immunology
  • Toxicology

Cite this

Partially-desulfated heparin improves survival in Pseudomonas pneumonia by enhancing bacterial clearance and ameliorating lung injury. / Sharma, Lokesh; Wu, Jiao; Patel, Vivek; Sitapara, Ravikumar; Rao, Narayanam V.; Kennedy, Thomas P.; Mantell, Lin L.

In: Journal of Immunotoxicology, Vol. 11, No. 3, 01.01.2014, p. 260-267.

Research output: Contribution to journalArticle

Sharma, Lokesh ; Wu, Jiao ; Patel, Vivek ; Sitapara, Ravikumar ; Rao, Narayanam V. ; Kennedy, Thomas P. ; Mantell, Lin L. / Partially-desulfated heparin improves survival in Pseudomonas pneumonia by enhancing bacterial clearance and ameliorating lung injury. In: Journal of Immunotoxicology. 2014 ; Vol. 11, No. 3. pp. 260-267.
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