Human monoclonal anti-endothelial cell IgG-derived from a systemic lupus erythematosus patient binds and activates human endotheliium in vitro.
Yazici, Zihni A. Raschi, E. Patel, Anjana Testoni, C. Borghi, M.O. Meroni, P.L. Lindsey, Nigel J.
Yazici, Zihni A.
Raschi, E.
Patel, Anjana
Testoni, C.
Borghi, M.O.
Meroni, P.L.
Lindsey, Nigel J.
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2001
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Abstract
Our objectives were to obtain monoclonal anti-endothelial cell antibodies (AECA) from systemic lupus erythematosus (SLE) patients, to characterize their antigen specificity, and their capability to induce a pro-inflammatory and pro-adhesive endothelial phenotype, and to investigate the mechanism of endothelial cell (EC) activation in vitro. Monoclonal IgG AECA were generated by hybridoma formation with human SLE B cells. Antigen specificity was characterized by immunoblotting with enriched cell membrane fractions, by cytofluorimetry and by cell solid-phase ELISA. Endothelial activation was evaluated by measuring increases in U937 cell adhesiveness, adhesion molecule (E-selectin and ICAM-1) expression and IL-6 production. In addition, mechanisms of endothelial activation were investigated by assessment of NF-B by measuring the loss of its inhibitor I-B. mAb E-3 bound live EC and recognized a 42 kDa EC membrane protein, it enhanced U937 adhesiveness, E-selectin and ICAM-1 expression and IL-6 production, and caused the loss of I-B. We conclude this is the first in vitro demonstration that a human monoclonal AECA from a SLE patient reacts with a constitutive endothelial membrane antigen and induces a pro-inflammatory endothelial phenotype through NF-B activation.
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Yazici ZA, Raschi E, Patel A, Testoni C, Borghi MO, Graham AM, Meroni PL and Lindsey N (2001) Human monoclonal anti-endothelial cell IgG-derived from a systemic lupus erythematosus patient binds and activates human endotheliium in vitro. International Immunology. 13(3): 349-357.
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