Intracellular complement activation-An alarm raising mechanism?

Area of Science:

• Immunology
• Cell Biology
• Metabolism

Background:

• The complement system is traditionally viewed as an extracellular defense mechanism.
• Recent findings indicate complement components are synthesized and activated within various cell types, not just the liver and macrophages.

Purpose of the Study:

• To explore the intracellular functions of the complement system.
• To understand the role of intracellular complement activation in cellular processes and immune responses.

Main Methods:

• Analysis of complement component production in diverse cell types (lymphocytes, adipocytes, epithelial cells).
• Investigation of intracellular complement activation (e.g., C3, C5) and its downstream effects.
• Examination of receptor-mediated signaling pathways involving complement activation products.

Main Results:

• Many cell types, including lymphocytes and adipocytes, produce complement components.
• Intracellular C3 and C5 activation in T cells impacts immunological tolerance and Th1 differentiation.
• Adipocytes uniquely produce complement sensors (C1q) and Factor D, crucial for alternative pathway amplification.
• Complement activation products signal through intracellular and cell membrane receptors (e.g., C3aR, C5aR1, C5aR2, MCP/CD46).

Conclusions:

• Intracellular complement activation has diverse roles, including antimicrobial defense, cell differentiation, and metabolic influence.
• Complement components act as intracellular alarm molecules, contributing to the cellular danger response.
• These findings link complement activation to cellular metabolism, intracellular defense, and adaptive immunity.