Activation of the alternative complement pathway by pneumococcal lipoteichoic acid.

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Cell wall teichoic acids activate the alternative complement pathway.
• The role of cell membrane lipoteichoic acid (LTA) in complement activation is not well understood.

Purpose of the Study:

• To investigate whether lipoteichoic acid (LTA) can activate the alternative complement pathway.
• To determine if LTA binds to erythrocytes and induces complement activation.

Main Methods:

• Radiolabelled pneumococcal LTA was incubated with sheep erythrocytes.
• Erythrocyte agglutination by a choline-specific myeloma protein (TEPC-15) confirmed LTA binding.
• Complement activation was assessed using guinea pig and human complement-deficient sera, followed by lysis assays.
• Immunoabsorption with TEPC-15 removed the sensitizing LTA.

Main Results:

• Pneumococcal LTA spontaneously bound to sheep erythrocytes in a temperature- and time-dependent manner.
• LTA-sensitized erythrocytes activated the alternative complement pathway, leading to cell lysis.
• The complement-activating property of LTA was confirmed to be due to the LTA molecule itself.

Conclusions:

• Purified pneumococcal LTA binds to erythrocytes.
• LTA binding to erythrocytes activates the alternative complement pathway.
• LTA is capable of initiating complement-mediated lysis of erythrocytes.