A role for CD54 (intercellular adhesion molecule-1) in leukocyte recruitment to the lung during the development of experimental idiopathic pneumonia syndrome.
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.
Gerbitz
Armin
A
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
Ewing
Patricia
P
Olkiewicz
Krystyna
K
Willmarth
Nicole E
NE
Williams
Debra
D
Hildebrandt
Gerhard
G
Wilke
Andrea
A
Liu
Chen
C
Eissner
Günther
G
Andreesen
Reinhard
R
Holler
Ernst
E
Guo
Renfeng
R
Ward
Peter A
PA
Cooke
Kenneth R
KR
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
D018799:Intercellular Adhesion Molecule-1