International Immunology, Vol 10, 861-868, Copyright © 1998 by Oxford University Press
Y Levy, B Gilburd, J George, N Del Papa, R Mallone, M Damianovich, M Blank, A Radice, Y Renaudineau, P Youinou, A Wiik, F Malavasi, PL Meroni and Y Shoenfeld
The IgG fraction of human anti-endothelial cell antibodies (AECA) obtained
from a patient with Wegener's granulomatosis was used as immunogen to raise
AECA mAb in mice selected among those which developed vasculitis-like
lesions after immunization. Three mAb (BGM, 3C8 and 7G2), selected by
cyto-ELISA and flow cytometry analyses, featured a specific reactivity with
human umbilical vein endothelial cells (HUVEC) and the mouse endothelial
cell line H5V; on the contrary, HEp2 cells, the murine melanoma B16 cell
line, the extracellular matrix as well as several other antigens tested
were not recognized. BGM mAb, an IgG3 precipitating a 70 kDa structure from
HUVEC, was able to induce endothelial cells to secrete amounts of IL-6
significantly higher than irrelevant controls or mAb binding different
endothelial antigens (i.e. CD31, CD29, ICAM-1 and HLA class I). BGM mAb
induced significant levels of antibody-dependent cell cytotoxicity (13 +/-
2.5 versus 0.6 +/- 0.03%). To the best of our knowledge, BGM is the first
murine mAb specific for human endothelial cells generated by idiotypic
manipulation; secondly, its biological properties further support the
notion of a pathogenic role for AECA in autoimmune-mediated diseases.
ARTICLES
Characterization of murine monoclonal anti-endothelial cell antibodies (AECA) produced by idiotypic manipulation with human AECA
Department of Medicine B, Tel-Hashomer and Sackler Faculty of Medicine, Tel-Aviv University, Sheba Medical Center, Israel.
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