Myeloperoxidase deficiency enhances inflammation after allogeneic marrow transplantation

Carlos Milla, Shuxia Yang, David N. Cornfield, Marie Luise Brennan, Stanley L. Hazen, Angela Panoskaltsis-Mortari, Bruce R. Blazar, Imad Y. Haddad

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Myeloperoxidase (MPO)-derived oxidants participate in the respiratory antimicrobial defense system but are also implicated in oxidant-mediated acute lung injury. We hypothesized that MPO contributes to lung injury commonly observed after bone marrow transplantation (BMT). MPO-sufficient (MPO+/+) and -deficient (MPO-/-) mice were given cyclophosphamide and lethally irradiated followed by infusion of inflammation-inducing donor spleen T cells at time of BMT. Despite suppressed generation of nitrative stress, MPO-/- recipient mice unexpectedly exhibited accelerated weight loss and increased markers of lung dysfunction compared with MPO+/+ mice. The increased lung injury during MPO deficiency was a result of donor T cell-dependent inflammatory responses because bronchoalveolar lavage fluids (BALF) from MPO-/- mice contained increased numbers of inflammatory cells and higher levels of the proinflammatory cytokine TNF-α and the monocyte chemoattractant protein-1 compared with wild-type mice. Enhanced inflammation in MPO-/- mice was associated with suppressed apoptosis of BALF inflammatory cells. The inflammatory process in MPO-/- recipients was also associated with enhanced necrosis of freshly isolated alveolar type II cells, critical for preventing capillary leak. We conclude that suppressed MPO-derived oxidative/nitrative stress is associated with enhanced lung inflammation and persistent alveolar epithelial injury.

Original languageEnglish (US)
Pages (from-to)L706-L714
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number4 31-4
DOIs
StatePublished - Oct 2004

Keywords

  • Alveolar type II cells
  • Apoptosis
  • Idiopathic pneumonia syndrome
  • Nitrotyrosine

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