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The modulation of human aortic endothelial cell ICAM-1 (CD-54) expression by serum containing high titers of anti-HLA antibodies.

Abstract：

:Allograft recipients who have preformed antibodies to MHC determinants or develop these antibodies post-transplantation have a higher incidence of cellular rejection and graft loss. It is unclear whether this association is an etiologic one or whether the presence of these antibodies solely identifies individuals with a more pronounced alloimmunologic response. To determine whether antibodies to MHC determinants have a direct role in enhancing cell-mediated immunity, specifically in altering effector-target cell adhesion, the expression of endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) in response to serum with high-titer anti-HLA antibodies was investigated. The target cells used were a pool of blood group O human aortic endothelial cells (HAECs) representing a wide range of HLA-A, B, C, and DR phenotypes. The test serum was serum pooled from 30 highly sensitized individuals (panel-reactive antibody 80%). Antibody binding to HAECs, and HAEC expression of class I and class II major histocompatibility (MHC) antigens and ICAM-1 were assessed by flow cytometry. General HAEC metabolic changes were assessed by 3H-uridine incorporation as a measure of RNA synthesis. Test serum resulted in almost a 14-fold increase in HAEC surface ICAM-1 expression compared with control serum, and titrations of test serum yielded a strong correlation between IgG bound to HAECs and HAEC ICAM-1 expression (r = 0.92). Test serum induced no change in expression of HAEC class I or class II MHC antigens, or 3H-uridine incorporation. The HAEC ICAM-1-inducing ability of the test serum was retained by concentrating the high molecular weight (> 100 kilodaltons) fraction of the test serum, isolation and purification of IgG from the test serum, and lost by absorbing this fraction with pooled platelets, suggesting that the activity was mediated by antibodies directed against MHC class I determinants. These data suggest that the presence of anti-HLA antibodies is more than a marker for individuals with greater alloreactive responsiveness. Anti-HLA antibodies may directly and specifically alter adhesion of effector cells to the allograft.

journal_name

Transplantation

journal_title

Transplantation

authors

Hosenpud JD,Shipley GD,Morris TE,Hefeneider SH,Wagner CR

subject

Has Abstract

pub_date

1993-02-01 00:00:00

pages

405-11

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

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The modulation of human aortic endothelial cell ICAM-1 (CD-54) expression by serum containing high titers of anti-HLA antibodies.