High mobility group box-1 mediates hyperoxia-induced impairment of Pseudomonas aeruginosa clearance and inflammatory lung injury in mice

Vivek Patel, Ravikumar A. Sitapara, Ashwini Gore, Binh Phan, Lokesh Sharma, Vaishali Sampat, Jian Hua Li, Huan Yang, Sangeeta S. Chavan, Haichao Wang, Kevin J. Tracey, Lin L. Mantell

Research output: Contribution to journalArticle

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Abstract

Mechanical ventilation with supraphysiological concentrations of oxygen (hyperoxia) is routinely used to treat patientswith respiratory distress.However, a significant number of patients on ventilators exhibit enhanced susceptibility to infections and develop ventilatorassociated pneumonia (VAP). Pseudomonas aeruginosa (PA) is one of the most common species of bacteria found in these patients. Previously, we demonstrated that prolonged exposure to hyperoxia can compromise the ability of alveolar macrophages (AMs), an essential part of the innate immunity, to phagocytose PA. This study sought to investigate the potentialmolecular mechanisms underlying hyperoxiacompromised innate immunity against bacterial infection in a murine model of PApneumonia.Here,we showthat exposure to hyperoxia (>99%O2) led to a significant elevation in concentrations of airway high mobility group box-1 (HMGB1) and increased mortality in C57BL/6 mice infected with PA. Treatment of these mice with a neutralizing anti-HMGB1 monoclonal antibody (mAb) resulted in a reduction in bacterial counts, injury, and numbers of neutrophils in the lungs, and an increase in leukocyte phagocytic activity compared with mice receiving controlmAb.This improved phagocytic function was associated with reduced concentrations of airway HMGB1. The correlation between phagocytic activity and concentrations of extracellular HMGB1 was also observed in cultured macrophages. These results indicate a pathogenic role for HMGB1 in hyperoxia-induced impairment with regard to a hostś ability to clear bacteria and inflammatory lung injury. Thus, HMGB1 may provide a novel molecular target for improving hyperoxia-compromised innate immunity in patients with VAP.

Original languageEnglish (US)
Pages (from-to)280-287
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume48
Issue number3
DOIs
StatePublished - Mar 1 2013

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Hyperoxia
Lung Injury
Pseudomonas aeruginosa
Bacteria
Innate Immunity
Macrophages
Monoclonal Antibodies
Oxygen
Pneumonia
Bacterial Load
Alveolar Macrophages
Mechanical Ventilators
Inbred C57BL Mouse
Phagocytosis
Artificial Respiration
Bacterial Infections
Neutrophils
Leukocytes
Lung
Mortality

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

High mobility group box-1 mediates hyperoxia-induced impairment of Pseudomonas aeruginosa clearance and inflammatory lung injury in mice. / Patel, Vivek; Sitapara, Ravikumar A.; Gore, Ashwini; Phan, Binh; Sharma, Lokesh; Sampat, Vaishali; Li, Jian Hua; Yang, Huan; Chavan, Sangeeta S.; Wang, Haichao; Tracey, Kevin J.; Mantell, Lin L.

In: American journal of respiratory cell and molecular biology, Vol. 48, No. 3, 01.03.2013, p. 280-287.

Research output: Contribution to journalArticle

Patel, V, Sitapara, RA, Gore, A, Phan, B, Sharma, L, Sampat, V, Li, JH, Yang, H, Chavan, SS, Wang, H, Tracey, KJ & Mantell, LL 2013, 'High mobility group box-1 mediates hyperoxia-induced impairment of Pseudomonas aeruginosa clearance and inflammatory lung injury in mice', American journal of respiratory cell and molecular biology, vol. 48, no. 3, pp. 280-287. https://doi.org/10.1165/rcmb.2012-0279OC
Patel, Vivek ; Sitapara, Ravikumar A. ; Gore, Ashwini ; Phan, Binh ; Sharma, Lokesh ; Sampat, Vaishali ; Li, Jian Hua ; Yang, Huan ; Chavan, Sangeeta S. ; Wang, Haichao ; Tracey, Kevin J. ; Mantell, Lin L. / High mobility group box-1 mediates hyperoxia-induced impairment of Pseudomonas aeruginosa clearance and inflammatory lung injury in mice. In: American journal of respiratory cell and molecular biology. 2013 ; Vol. 48, No. 3. pp. 280-287.
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