Cerebral endothelial expression of adhesion molecules in mice with chronic graft-versus-host disease.
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.
Sostak
Petra
P
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistr 15, 81377 Munich, Germany. Petra.Sostak@nro.med.uni-muenchen.de
Reich
Petra
P
Padovan
Claudio S
CS
Gerbitz
Armin
A
Holler
Ernst
E
Straube
Andreas
A
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
D019010:Vascular Cell Adhesion Molecule-1; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1