NADPH oxidase in bone marrow-derived cells mediates pulmonary ischemia-reperfusion injury

Zequan Yang, Ashish K. Sharma, Melissa Marshall, Irving L. Kron, Victor E. Laubach

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Reactive oxygen species (ROS) play a crucial role in ischemia-reperfusion (IR) injury after lung transplantation. We hypothesized that NADPH oxidase derived from bone marrow (BM) cells contributes importantly to lung IR injury. An in vivo mouse model of lung IR injury was employed. Wild-type C57BL/6 (WT) mice, p47 phox knockout (p47 phox-/-) mice, or chimeras created by BM transplantation between WT and p47 phox-/-mice were assigned to either Sham (left thoracotomy) or six study groups that underwent IR (1 h left hilar occlusion and 2 h reperfusion). After reperfusion, pulmonary function was assessed using an isolated, buffer-perfused lung system. Lung injury was assessed by measuring vascular permeability (via Evans blue dye), edema, neutrophil infiltration (via myeloper oxidase [MPO]), lipid peroxidation (via malondialdyhyde [MDA]), and expression of proinflammatory cytokines. Lung IR resulted in significantly increased MDA in WT mice, indicative of oxidative stress. WT mice treated with apocynin (an NADPH oxidase inhibitor) and p47 phox-/-mice displayed significantly reduced pulmonary dysfunction and injury (vascular permeability, edema, MPO, and MDA). In BM chimeras, significantly reduced pulmonary dysfunction and injury occurred after IR in p47 phox-/-→WT chimeras (donor/recipient) but not WT→ p47 phox-/-chimeras. Induction of TNF-;, IL-17, IL-6, RANTES (CCL5), KC (CXCL1), MIP-2 (CXCL2), and MCP-1 (CCL2) was significantly reduced after IR in NADPH oxidase-deficient mice and p47 phox-/-→WT chimeras but not WT→p47 phox-/-chimeras. These results indicate that NADPH oxidase-generated ROS specifically from BM-derived cells contributes importantly to lung IR injury. NADPH oxidase may represent a novel therapeutic target for the treatment of IR injury after lung transplantation.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume40
Issue number3
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Keywords

  • Bone marrow transplant
  • Lung ischemia-reperfusion injury
  • NADP
  • Reactive oxygen species

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'NADPH oxidase in bone marrow-derived cells mediates pulmonary ischemia-reperfusion injury'. Together they form a unique fingerprint.

  • Cite this