Objective. To investigate the ability of human anti-&-glycoprotein I (anti-&GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.Methods. Six human affinity-purified polyclonal anti-P,GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent f3,GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F,, (6-keto-PGF1,) secretion.Results. The affinity-purified IgG and the MAb with anti-&GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human P,GPI. After EC binding, both polycJonaJ and monoclonal antibodies up-regulated adhesion molecule expres-

Objective. To elucidate the role of antiendothelial cell antibodies (AECA) in vascular inflammation in patients with Wegener's granulomatosis (WG). Methods. IgG fractions from 3 AECA‐positive WG patients, IgG from 3 AECA‐negative WG patients, and IgG from healthy donors were tested for their ability to: a) bind to endothelial cells and to display complement‐dependent or antibody‐dependent cellular cytotoxicity, b) modulate cell membrane expression of adhesion molecules, as evaluated by cytofluorometry and by immunoenzymatic assay, and c) induce the secretion of interleukin‐1β (IL‐1β), IL‐6, IL‐8, and monocyte chemotactic protein 1 (MCP‐1). Results. We found that AECA IgG from WG patients do not display any significant cytotoxicity but are able to up‐regulate the expression of E‐selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 and to induce the secretion of IL‐1β, IL‐6, IL‐8, and MCP‐1. Conclusion. AECA in patients with WG could play a potential pathogenetic role by activating endothelial cells, and thus facilitating leukocyte recruitment and adhesion to endothelial surfaces, rather than by displaying a cytotoxic activity.