Importance of endothelial VCAM-1 for inflammatory leukocytic infiltration in vivo.
The microvascular endothelia of rejecting DBA/2----C57B1/6 murine cardiac allografts develop reactivity with the mAb M/K-2, which recognizes the murine homologue of the human leukocyte adhesion molecule VCAM-1. This reactivity does not develop in DBA/2----DBA/2 cardiac isografts or normal DBA/2 cardiac tissues. To determine whether endothelial VCAM-1 plays a role in allograft inflammation, cardiac allograft recipients were treated with M/K-2 antibody and monitored for leukocytic graft infiltration and graft survival. Treatment of the graft recipients with 200 micrograms/day M/K-2 Ig prolonged graft survival by 5 to 6 days (statistically significant); whereas treatment with 100 micrograms M/K-2 Ig every other day after transplant did not influence graft survival. Neither treatment interfered with leukocytic infiltration, as detected histologically or by limiting dilution analysis. The high dose treatment, but not the low dose treatment, resulted in high circulating levels of M/K-2, as detected by serum ELISA, and prominent antibody deposition on the graft vascular endothelia, as demonstrated by immunohistologic analysis. These data demonstrate that VCAM-1 is uniquely expressed on the vascular endothelia of rejecting murine cardiac allografts, and that a mAb to VCAM-1 can interfere with the allograft rejection process. Although this antibody can interfere with lymphocyte-endothelial adhesion in vitro, it has little effect on leukocytic infiltration in rejecting allografts suggesting that this process does not depend exclusively on VCAM-1 expression.
Pelletier
R P
RP
Department of Surgery, Ohio State University College of Medicine, Columbus 43210.
Ohye
R G
RG
Vanbuskirk
A
A
Sedmak
D D
DD
Kincade
P
P
Ferguson
R M
RM
Orosz
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation; D007249:Inflammation / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1