What activates the lectin complement system?

Activation of the Lectin Complement System

The lectin complement pathway is primarily activated by the binding of pattern recognition molecules such as mannose-binding lectin (MBL) and ficolins to carbohydrate structures on pathogen surfaces. 1

Key Activators of the Lectin Pathway

Pattern Recognition Molecules

• Mannose-binding lectin (MBL): Recognizes specific carbohydrate patterns arranged in particular geometries on microbial surfaces 2
• Ficolins: Three types in humans 1:
  • L-ficolin (ficolin-2)
  • H-ficolin (ficolin-3)
  • M-ficolin (ficolin-1)

Activation Mechanisms

1. Recognition step: MBL or ficolins bind to carbohydrate structures on pathogen surfaces 1
2. Complex formation: These pattern recognition molecules circulate in blood complexed with MBL-associated serine proteases (MASPs) 1
3. Proteolytic cascade: Upon binding to pathogens, the MASPs become activated, particularly:
   • MASP-2: Activates C4 and C2 components
   • MASP-1: Activates C2 and enhances MASP-2 activation
   • MASP-3: Role not fully defined but involved in alternative pathway 1

Specific Pathogen Structures Recognized

• Gram-positive bacteria: L-ficolin specifically binds to lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae 3
• Various microorganisms: MBL recognizes carbohydrate patterns found on many pathogens, including bacteria, fungi, and viruses 4

Clinical Significance

• Sepsis: Microorganisms and damage-associated molecular patterns (DAMPs) can initiate the lectin pathway, contributing to the inflammatory and coagulation cascades in sepsis 5
• Hereditary Angioedema: C1-inhibitor deficiency affects regulation of the lectin pathway, contributing to disease pathophysiology 6
• Immune defense: Deficiencies in lectin pathway components are associated with increased susceptibility to infections, highlighting its importance in innate immunity 1

Downstream Effects

• Once activated, the lectin pathway leads to:
  • Formation of C3 convertase through C4 and C2 activation
  • Complement cascade activation
  • Opsonization of pathogens
  • Enhancement of phagocytosis
  • Inflammatory response
  • Potential activation of the coagulation system 1

The lectin pathway represents a critical first-line defense mechanism in innate immunity, recognizing and responding to pathogenic threats before adaptive immunity can be mobilized.