Implications of de novo ELAM-1 and VCAM-1 expression in human cardiac allograft rejection.
Both cytokines produced by activated monocytes and T cells and direct cell-to-cell contact with antigen-primed T cells during inflammatory reactions are known to induce the expression of several adhesion proteins on endothelial cells. In this prospective longitudinal study, we analyzed the expression of ELAM-1, VCAM-1, and ICAM-1 on myocardial allograft biopsy specimens taken from 16 cardiac allograft recipients either for routine monitoring or for the investigation of suspected rejection. Infiltrating T cells were identified using anti-CD3 antibodies. Three to six sequential biopsies taken at one-week intervals were analyzed by means of conventional histology and immunohistochemistry. Seven patients did not develop rejection during the study; their biopsies were negative for VCAM-1 and ELAM-1, although faint ICAM-1 staining was present on capillaries, reflecting constitutive expression. Three patients entered the study with clear-cut clinical and histologic signs of acute rejection. Intense VCAM-1 and ICAM-1 expression was detected on capillary and postcapillary venules, together with a heavy CD3+ T cell infiltrate; VCAM-1 was also expressed on arteriolar endothelial cells. ELAM-1 was undetectable in all three cases. Six patients developed acute rejection during the course of the study. In four, ELAM-1 and VCAM-1 were expressed on both capillary and postcapillary venules one or two weeks before the histological diagnosis of rejection (heavy CD3+ cell infiltrate). Importantly, ELAM-1 expression was short-lived and had disappeared by the time CD3+ cellular infiltrate was detected, thus extending in vivo the finding that ELAM-1 expression is usually transient in vitro. Only VCAM-1 expression was observed in the other two patients, one week prior to the histological diagnosis of rejection. These results suggest that ELAM-1 and VCAM-1 might represent early predictive markers of acute cardiac allograft rejection. ELAM-1 expression is, however, usually transient, necessitating frequent testing.
Ferran
C
C
INSERM U-25, Hôpital Necker, Paris, France.
Peuchmaur
M
M
Desruennes
M
M
Ghoussoub
J J
JJ
Cabrol
A
A
Brousse
N
N
Cabrol
C
C
Bach
J F
JF
Chatenoud
L
L
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D017252:CD3 Complex / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood / Q000502:physiology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology; D006084:Graft Rejection / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D006684:HLA-DR Antigens / Q000097:blood; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1
D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D019010:Vascular Cell Adhesion Molecule-1