title: A role for CD54 (intercellular adhesion molecule-1) in leukocyte recruitment to the lung during the development of experimental idiopathic pneumonia syndrome.
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-alpha 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.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Gerbitz
authors.forename: Patricia
authors.initials: P
authors.lastname: Ewing
authors.forename: Krystyna
authors.initials: K
authors.lastname: Olkiewicz
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Willmarth
authors.forename: Debra
authors.initials: D
authors.lastname: Williams
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hildebrandt
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilke
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Günther
authors.initials: G
authors.lastname: Eissner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002465:Cell Movement; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000209:etiology*; D014184:Transplantation, Homologous
chemical_list: D018799:Intercellular Adhesion Molecule-1