title: Cerebral endothelial expression of adhesion molecules in mice with chronic graft-versus-host disease.
abstract: OBJECTIVE
  Graft-versus-host disease (GvHD) is a major complication after allogeneic bone marrow transplantation (BMT). The theory that the central nervous system (in addition to the peripheral nervous system) participates in GvHD has been supported by detection of cerebral lymphomononuclear infiltrates in experimental GvHD and the observation of cerebral angiitis-like disease in patients with chronic GvHD.
  
  
  METHODS
  In a murine BMT model, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on cerebral endothelium after allogeneic and syngeneic transplantation. Through the use of ICAM-1-knockout mice, the effect of ICAM-1 deficiency on cellular infiltration was evaluated. As an indicator of enhanced apoptotic cell death, we examined the cerebral expression of Fas antigen (Fas), the occurrence of the poly-ADP ribose polymerase p85 fragment, and the distribution of TUNEL positive-stained cells.
  
  
  RESULTS
  In close correlation with earlier findings of cerebral infiltration in the same animals, we found cerebral endothelial upregulation of ICAM-1 and especially of VCAM-1 in allogeneic recipients compared with syngeneic animals without GvHD and unmanipulated controls. In ICAM-1-knockout mice, leukocytic infiltration did not differ from that in wild-type animals. Neither cerebral histopathologic changes nor an apoptotic effect of cellular infiltrates on brain parenchyma could be detected.
  
  
  CONCLUSIONS
  In this model of experimental GvHD, VCAM-1 may play a critical role in leukocyte recruitment into the central nervous system of animals with chronic GvHD.
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistr 15, 81377 Munich, Germany. Petra.Sostak@nro.med.uni-muenchen.de
authors.forename: Petra
authors.initials: P
authors.lastname: Sostak
authors.forename: Petra
authors.initials: P
authors.lastname: Reich
authors.forename: Claudio S
authors.initials: CS
authors.lastname: Padovan
authors.forename: Armin
authors.initials: A
authors.lastname: Gerbitz
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Andreas
authors.initials: A
authors.lastname: Straube
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016026:Bone Marrow Transplantation; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1