Complement activation by interaction of polyanions and polycations

Area of Science:

• Immunology
• Biochemistry

Background:

• Heparin-protamine interactions in serum activate the primary complement pathway and deplete early complement components.
• The roles of heparin-protamine complexes, immunoglobulins, C1q, and C1 inhibitor (C1-INH) in this activation were investigated.

Purpose of the Study:

• To elucidate the mechanisms of complement activation by heparin-protamine complexes.
• To determine the involvement of specific complement components and regulatory proteins.

Main Methods:

• Studied heparin-protamine complex formation in serum and buffer.
• Assessed complement consumption in normal and hypogammaglobulinaemic sera.
• Investigated the role of C1q and immunoglobulins in complement activation.

Main Results:

• Heparin and protamine formed complexes that induced maximal complement consumption at optimal precipitation proportions.
• Complexes contained C1q and IgG, but immunoglobulins were not required for activation.
• Maximal consumption occurred with transient reactivity to C1, likely at the C1q level.
• Free heparin potentiated C1 inhibitor activity, limiting consumption.

Conclusions:

• Complement consumption by heparin-protamine complexes involves transient interaction with C1, primarily at the C1q level.
• The process is influenced by heparin's potentiation of C1 inhibitor and direct effects on early complement components.
• These interactions may initiate inflammatory reactions through direct complement system activation.