TREATMENT OF MICE WITH ANTI-CD3 MAB INDUCES ENDOTHELIAL VASCULAR CELL-ADHESION MOLECULE-1 EXPRESSION

被引:20
作者
BERGESE, SD
PELLETIER, RP
OHYE, RG
VALLERA, DA
OROSZ, CG
机构
[1] OHIO STATE UNIV,COLL MED,DEPT PATHOL,COLUMBUS,OH 43210
[2] OHIO STATE UNIV,COLL MED,DEPT PHARMACOL,COLUMBUS,OH 43210
[3] UNIV MINNESOTA,DEPT THERAPEUT RADIOL,MINNEAPOLIS,MN 55455
[4] OHIO STATE UNIV,COLL MED,DEPT SURG,COLUMBUS,OH 43210
关键词
D O I
10.1097/00007890-199403150-00013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In vivo treatment of mice with anti-CD3 mAb causes polyclonal T cell activation and cytokine release. Since several cytokines are known to alter expression of MHC molecules and adhesion molecules on endothelia, we hypothesized that anti-CD3 mAb treatment should result in activation of vascular endothelia. In previous studies, we established that vascular endothelial cells in murine heterotopic cardiac grafts can develop at least 2 stable inflammatory phenotypes: cardiac allograft endothelia characteristically develop reactivity with MECA-32 mAb (undefined endothelial epitope) and M/K-2 mAb (murine vascular cell adhesion molecule-1 [VCAM-1]), whereas cardiac isografts develop reactivity with MECA-32, but not M/K-2 mAb. We now report that a single treatment of cardiac isograft recipients with the anti-CD3 mAb 145-2C11 caused expression of VCAM-1 on all cardiac isograft endothelia, including the microvascular endothelia. In contrast, expression of endothelial VCAM-1 in the native heart of the isograft recipient was limited to patchy areas of larger arteries. This patchy, arterial pattern of VCAM-1 expression was observed in lung, liver, kidney, and thymus of all mice treated with 145-2C11, whether or not they were implanted with a cardiac isograft, and was dissociated from expression of MECA-32 mAb reactivity. Hence, treatment of mice with anti-CD3 mAb causes systemic endothelial activation (VCAM-1 expression), and endothelial cells of recently implanted cardiac isografts appear to be by. hypersensitive to induction of VCAM-1 by anti-CD3 mAb treatment. Further studies showed that (1) treatment with 145-2C11 F(ab)'(2) fragments did not induce endothelial activation, (2) intravenous pretreatment with pentoxifylline eliminated all endothelial effects of 145-2C11 treatment, (3) induction of endothelial activation by 145-2C11 mAb always paralleled the expression of adverse physiologic symptoms, and (4) mice exhibit strain specific differences in endothelial responses to 145-2C11 treatment. We propose that anti-CD3 mAb treatment causes simultaneous activation of circulating T cells and systemic vascular endothelial cells which may facilitate systemic lymphocyte endothelial interactions, and may explain the rapid disappearance of T cells from the circulation that is associated with anti-CD3 treatment in mouse and man.
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收藏
页码:711 / 717
页数:7
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