Role of selectin-dependent adhesion in cardiac allograft rejection.
BACKGROUND
Selectins play important roles in the inflammatory responses by eliciting leukocyte rolling. The roles of E- and P-selectins in the acute rejection of cardiac allografts remain unclear. This study was designed to evaluate whether E- and P-selectins participate in the pathophysiology of heart rejection.


METHODS
Heterotopic heart transplantation was performed in both mice and rats in full histoincompatibility combinations. Immunohistochemistry, flow-cytometry, and reverse transcriptase- polymerase chain reaction were performed to evaluate E-, P-selectin and sialyl Lewis X (SLeX) expression in rejecting cardiac allografts. The effects of short-term administration of monoclonal antibodies (mAbs) to E- and P-selectins on cardiac allograft survival were also evaluated.


RESULTS
Significant prolongation of graft survival was observed in mice treated with either anti-E- or P-selectin mAbs, or both. The enhanced endothelial and mRNA expression of E- and P-selectins was observed in the rejecting cardiac allografts. Some graft- infiltrating mononuclear cells were double-stained with both anti-SLeX and anti-alphabetaT cell receptor mAbs. Flow-cytometric analysis of graft-infiltrating cells also showed enhanced SLeX expression.


CONCLUSIONS
These results suggest that both P- and E-selectins are critically involved in the early development of acute heart rejection.
Yamazaki
S
S
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Isobe
M
M
Suzuki
J
J
Tojo
S
S
Horie
S
S
Okubo
Y
Y
Sekiguchi
M
M
D000818:Animals; D019040:E-Selectin / Q000502:physiology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007957:Leukocyte Adherence Inhibition Test; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D019007:P-Selectin / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic / Q000276:immunology* / Q000473:pathology
D019040:E-Selectin; D019007:P-Selectin