The regulation of proresolving lipid mediator profiles in baboon pneumonia by inhaled carbon monoxide

Jesmond Dalli, Bryan D. Kraft, Romain A. Colas, Masakazu Shinohara, Laura E. Fredenburgh, Dean R. Hess, Nan Chiang, Karen Welty-Wolf, Augustine M. Choi, Claude A. Piantadosi, Charles N. Serhan

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Strategies for the treatment of bacterial pneumonia beyond traditional antimicrobial therapy have been limited. The recently discovered novel genus of lipid mediators, coined "specialized proresolving mediators" (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of inflammation. We performed lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae-infected (n =5-6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide (CO) at 48 hours (200-300 ppm for 60-90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory LM signature profile with elevated leukotriene B4 and prostaglandins. Plasma from baboons with S. pneumoniae pneumonia also displayed significantly reduced LM-SPM levels, including eicosapentaenoic acid-derived E-series resolvins (RvE) and lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to pneumonia resolution.

Original languageEnglish (US)
Pages (from-to)314-325
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume53
Issue number3
DOIs
StatePublished - Sep 1 2015

Keywords

  • Bacterial
  • Inflammation resolution
  • Pneumonia
  • Therapeutic carbon monoxide

ASJC Scopus subject areas

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

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