Human astrocytes express membrane cofactor protein (CD46), a regulator of complement activation

Area of Science:

• Neuroimmunology
• Complement biology
• Cellular immunology

Background:

• Astrocytes play crucial roles in central nervous system immunity.
• The complement system is a key component of innate immunity with implications in neurological diseases.
• Understanding complement regulatory protein expression on astrocytes is vital for neuroinflammatory research.

Purpose of the Study:

• To investigate the expression and function of complement regulatory proteins, specifically membrane cofactor protein (CD46), on human astrocytes.
• To determine if astrocyte CD46 expression is altered during viral infection, such as by cytomegalovirus.

Main Methods:

• Indirect immunofluorescence microscopy and flow cytometry were used to detect CD46 expression on cultured human astrocytes.
• Western transfer and immunoblotting identified the molecular weight of CD46.
• Analysis of astrocyte messenger RNA (mRNA) identified alternatively spliced CD46 transcripts.
• Expression of decay accelerating factor and type 1 complement receptor was also assessed.

Main Results:

• Human astrocytes express membrane cofactor protein (CD46), detected as a doublet of Mr 66,000 and 56,000.
• Multiple alternatively spliced CD46 transcripts were found in astrocytes.
• Astrocytes express decay accelerating factor but not the type 1 complement receptor.
• Cytomegalovirus infection led to the upregulation of CD46 expression on astrocytes.

Conclusions:

• Astrocytes express key proteins, including CD46 and decay accelerating factor, that regulate complement activation.
• Astrocyte CD46 expression is upregulated following cytomegalovirus infection.
• These findings suggest that astrocytes possess mechanisms to protect themselves against autologous complement-mediated damage.