Complement proteins in unexpected places: why we should be excited, not concerned!

Area of Science:

• Immunology
• Cell Biology

Background:

• The complement system is a crucial immune defense mechanism involving over 30 plasma and cell surface proteins.
• Traditionally, hepatocytes were considered the primary source of complement components, which are then released into circulation.

Purpose of the Study:

• To address the ongoing debate regarding the intracellular activation of complement proteins.
• To advocate for the acceptance and exploration of novel scientific findings that challenge established paradigms in complement research.

Main Methods:

• This opinion article reviews existing evidence on extrahepatic synthesis of complement proteins.
• It discusses recent findings on intracellular complement activation and their implications.

Main Results:

• Substantial evidence supports the extrahepatic synthesis of complement proteins by various cell types, including immune cells, epithelial cells, fibroblasts, and neuronal cells.
• Emerging research indicates that certain complement proteins can be activated within intracellular compartments, a notion met with resistance in some scientific circles.

Conclusions:

• The discovery of intracellular complement activation, despite initial skepticism, highlights the need to embrace new findings that may reshape our understanding of immune system function.
• Encouraging the investigation of such paradigm-shifting discoveries is essential for scientific progress in immunology and beyond.