A Role for TNF Receptor Type II in Leukocyte Infiltration into the Lung during Experimental Idiopathic Pneumonia Syndrome

Gerhard C. Hildebrandt, Krystyna M. Olkiewicz, Leigh Corrion, Shawn G. Clouthier, Elizabeth M. Pierce, Chen Liu, Kenneth R. Cooke

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication following allogeneic stem cell transplantation (allo-SCT). Experimental models have revealed that TNF-α contributes to pulmonary vascular endothelial cell (EC) apoptosis, and modulates the infiltration of donor leukocytes into the lung parenchyma. The inflammatory effects of TNF-α are mediated by signaling through the type I (TNFRI) or type II (TNFRII) TNF receptors. We investigated the relative contribution of TNFRI and TNFRII to leukocyte infiltration into the lung following allo-SCT by using established murine models. Wild-type (wt) B6 mice or B6 animals deficient in either TNFRI or TNFRII were lethally irradiated and received SCT from allogeneic (LP/J) or syngeneic (B6) donors. At week 5 following SCT, the severity of IPS was significantly reduced in TNFRII-/- recipients compared to wt controls, but no effect was observed in TNFRI-/- animals. Bronchoalveolar lavage fluid (BALF) levels of RANTES and pulmonary ICAM-1 expression in TNFRII-/- recipients were also reduced, and correlated with a reduction of CD8+ cells in the lung. Pulmonary inflammation was also decreased in TNFRII-/- mice using an isolated MHC class I disparate model (bm1 → B6), and in bm1 wt mice transplanted with B6 TNF-α-/- donor cells. Collectively, these data demonstrate a role for TNF-α signaling through TNFRII in leukocyte infiltration into the lung following allo-SCT, and suggest that disruption of the TNF-α:TNFRII pathway may be an effective tool to prevent or treat IPS.

Original languageEnglish (US)
Pages (from-to)385-396
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Transplantation
  • Hematology

Keywords

  • Cytokines
  • Graft-versus-host disease
  • Stem cell transplantation
  • TNF-α

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