J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/05/1619/10 $2.00
Volume 185, Number 9, May 5, 1997 1619-1628

The Cytolytically Inactive Terminal Complement Complex Activates Endothelial Cells to Express Adhesion Molecules and Tissue Factor Procoagulant Activity

By Francesco Tedesco,^* Mario Pausa, Ermanno Nardon,^* Martino Introna,^§ Alberto Mantovani,^§ and Aldo Dobrina^*

From ^* Dipartimento di Fisiologia e Patologia and  Istituto di Ginecologia ed Ostetricia, Università di Trieste, Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo", Trieste, Italy; ^§ Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; and  Dipartimento di Biotecnologia, Sezione di Patologia ed Immunologia, Università di Brescia, Brescia, Italy

The membrane attack complex of complement (C) in sublytic concentrations stimulates endothelial cells (EC) to express adhesion molecules and to release biologically active products. We have examined the ability of a cytolytically inactive form of this complex, which is incapable of inserting into the cell membrane, to upregulate the expression of adhesion molecules and of tissue factor (TF) procoagulant activity. The inactive terminal C complex (iTCC) was prepared by mixing C5b6, C7, C8, and C9 and was purified by fast protein liquid chromatography on a Superose 12 column. Binding of this complex to EC was found to be dose dependent and was inhibited by anti-C9 antibodies, as assessed both by ELISA using an mAb anti-C9 neoantigen and by measuring cell-bound ¹²⁵I-labeled iTCC. Exposure of EC to iTCC resulted in a dose- and time-dependent expression of endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 accompanied by increased levels of the corresponding mRNA, but not in the rapid expression of P-selectin. Inactive TCC also induced increased TF activity evaluated by a chromogenic assay that measures the formation of factor Xa. These effects were inhibited by anti-C9 antibodies. The data support the conclusion that iTCC may induce proinflammatory and procoagulant activities on EC.

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