The cytolytically inactive terminal complement complex activates endothelial cells to express adhesion molecules and...

Area of Science:

• Immunology
• Cell Biology
• Complement System

Background:

• The complement system's Membrane Attack Complex (MAC) typically causes cell lysis.
• Sublytic MAC concentrations stimulate endothelial cells (EC) to express adhesion molecules and release bioactive products.
• The procoagulant activity of EC is linked to inflammation and thrombosis.

Purpose of the Study:

• To investigate the effects of a cytolytically inactive form of the MAC (iTCC) on EC.
• To determine if iTCC can upregulate adhesion molecule expression and tissue factor (TF) procoagulant activity.
• To understand the mechanisms by which iTCC influences EC function.

Main Methods:

• Preparation and purification of inactive terminal C complex (iTCC) using C5b6, C7, C8, and C9.
• Assessment of iTCC binding to EC using ELISA and 125I-labeled iTCC, with inhibition studies using anti-C9 antibodies.
• Measurement of adhesion molecule expression (ELAM-1, ICAM-1, VCAM-1) and TF activity in EC exposed to iTCC.

Main Results:

• iTCC bound to EC in a dose-dependent manner, inhibited by anti-C9 antibodies.
• Exposure to iTCC induced dose- and time-dependent expression of ELAM-1, ICAM-1, and VCAM-1, with increased mRNA levels.
• iTCC also significantly increased TF procoagulant activity, an effect also blocked by anti-C9 antibodies.

Conclusions:

• A cytolytically inactive form of the MAC (iTCC) can activate endothelial cells.
• iTCC induces proinflammatory (adhesion molecules) and procoagulant (TF activity) responses in EC.
• These findings suggest a novel role for non-lytic complement complexes in vascular inflammation and thrombosis.