Human glomerular epithelial cells synthesize and secrete the third component of complement

Area of Science:

• Immunology
• Nephrology
• Molecular Biology

Background:

• Complement proteins are primarily synthesized by hepatocytes.
• Recent findings indicate complement synthesis by various cell types in different tissues.
• The role of locally produced complement in kidney physiology and pathology is an area of active investigation.

Purpose of the Study:

• To investigate the synthesis and secretion of the third component of complement (C3) by cultured glomerular epithelial cells (GEC).
• To determine the regulatory effects of proinflammatory cytokines on C3 secretion by GEC.
• To examine the expression of complement regulatory proteins in GEC.

Main Methods:

• Reverse transcriptase polymerase reaction (RT-PCR) to detect C3 mRNA expression in GEC and whole kidney.
• Enzyme-linked immunosorbent assay (ELISA) to quantify C3 secretion in GEC culture supernatants.
• Cytokine treatment of GEC to assess effects on C3 and regulatory protein expression.

Main Results:

• GEC express C3 mRNA and secrete C3 protein.
• Proinflammatory cytokines, particularly IL-1 beta, significantly upregulate C3 secretion from GEC.
• GEC express complement regulatory proteins MCP, DAF, CR-1, and CD59.
• Cytokine treatment did not alter MCP, DAF, or CR-1 expression but increased CD59 expression.

Conclusions:

• Cultured glomerular epithelial cells synthesize and secrete C3.
• Local C3 production in the glomerulus is regulated by inflammatory cytokines and may contribute to complement activation and glomerular injury.
• The differential expression of complement regulatory proteins in GEC suggests a role in modulating local complement activity during inflammation.