Membrane vesiculation protects erythrocytes from destruction by complement

Area of Science:

• Immunology
• Cell Biology
• Complement System

Background:

• Nucleated cells resist complement (C) attack via exocytosis/endocytosis of the membrane attack complex (MAC).
• The one-hit theory posits that a single MAC channel on erythrocytes (E) leads to lysis.
• Existing complement regulatory proteins (CD59, C8bp/HRF) prevent MAC assembly.

Purpose of the Study:

• To investigate if erythrocytes possess mechanisms to eliminate MAC and escape complement-mediated lysis.
• To determine the role of calcium (Ca2+) in MAC elimination and erythrocyte protection.

Main Methods:

• Incubation of human and guinea pig erythrocytes (E) and SRBC with C5b-9 (MAC).
• Monitoring of vesiculation and cell lysis in response to MAC attack.
• Quantification of Ca2+ influx and its effect on vesiculation and lysis.
• Analysis of MAC component (C9) enrichment in released vesicles.

Main Results:

• Human and guinea pig E, but not SRBC, eliminate MAC via microvesicle release, preventing lysis.
• Vesiculation occurs without a lag phase and is Ca2+ influx-dependent.
• Increased Ca2+ concentration correlates with increased vesiculation and decreased lysis.
• Released vesicles from guinea pig E are significantly enriched in C9.

Conclusions:

• Erythrocytes possess a Ca2+-dependent mechanism to eliminate MAC through vesiculation, providing protection from complement-mediated lysis.
• This MAC elimination pathway complements known regulatory proteins like CD59 and C8bp/HRF.
• Selective MAC elimination represents a novel host defense strategy against complement attack.