A role for CD54 (intercellular adhesion molecule-1) in leukocyte recruitment to the lung during the development of experimental idiopathic pneumonia syndrome

Armin Gerbitz, Patricia Ewing, Krystyna Olkiewicz, Nicole E. Willmarth, Debra Williams, Gerhard Hildebrandt, Andrea Wilke, Chen Liu, Günther Eissner, Reinhard Andreesen, Ernst Holler, Renfeng Guo, Peter A. Ward, Kenneth R Cooke

Research output: Contribution to journalArticle

Abstract

Background. Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication of allogeneic bone marrow transplantation (BMT). IPS is associated with elevated bronchoalveolar lavage (BAL) fluid levels of tumor necrosis factor-α and lipopolysaccharide, both of which are potent activators of endothelial cells (ECs). EC expression of the adhesion molecule CD54 (intercellular adhesion molecule [ICAM]-1) has been shown to be a major regulator of pulmonary inflammation in various experimental models. Methods. Using a well-established murine BMT system in which lung injury and graft-versus-host disease (GvHD) are induced by minor histocompatibility antigenic differences between donor and host, the RNase Protection Assay, mice deficient in ICAM-1 expression, and a monoclonal blocking antibody to ICAM, we evaluated the role of the pulmonary vascular expression of CD54 in the development of IPS. Results. Enhanced pulmonary vascular expression of ICAM-1 coincided with the development of IPS. When ICAM-1 -/- mice were used as allogeneic BMT recipients, IPS severity (measured by lung histopathology, BAL cellularity, and cytokine expression) was significantly reduced compared with wild-type controls. Similar results were also observed when wild-type recipients were treated with a monoclonal blocking antibody to ICAM-1. Surprisingly, ICAM-1 had differential effects on leukocyte infiltration into GvHD target organs; ICAM-1 deficiency had no impact on intestinal histopathology, whereas ICAM-1 -/- BMT recipients had significantly enhanced hepatic injury. Conclusions. These data demonstrate that although the expression of ICAM-1 is critical for the development of IPS, different mechanisms of leukocyte recruitment are operative in other GvHD target organs.

Original languageEnglish (US)
Pages (from-to)536-542
Number of pages7
JournalTransplantation
Volume79
Issue number5
DOIs
Publication statusPublished - Mar 15 2005
Externally publishedYes

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Keywords

  • Bone marrow transplantation
  • Cytokines
  • Endothelium
  • Graft-versus-host disease

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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