The chemotactic receptor for human C5a anaphylatoxin

Area of Science:

• Immunology
• Cell Biology

Background:

• Host defense and inflammation involve receptor-mediated events initiated by chemotactic factors.
• Complement receptors CR1 and CR3 mediate neutrophil phagocytosis and adhesion.
• The C5a receptor mediates pro-inflammatory and chemotactic actions of complement anaphylatoxin C5a.

Purpose of the Study:

• To clone and characterize the human C5a receptor.
• To understand the role of the C5a receptor in neutrophil function and inflammatory responses.
• To investigate the potential in vivo involvement of the C5a receptor in shock conditions.

Main Methods:

• Cloning of the human C5a receptor from U937 and HL-60 cells.
• Identification via high-affinity binding assays in COS-7 cells expressing the receptor.
• Deduction of the amino-acid sequence to identify functional motifs.

Main Results:

• The human C5a receptor was successfully cloned and identified.
• The C5a receptor stimulates neutrophil chemotaxis, granule release, and superoxide production.
• It also upregulates MAC-1 and CR1 expression/activity while decreasing MEL-14 on neutrophils.
• The deduced amino-acid sequence contains motifs for GTP-binding protein interaction.

Conclusions:

• The human C5a receptor plays a significant role in modulating neutrophil functions during inflammatory responses.
• Its actions contribute to host defense mechanisms and potentially to pathological conditions like septic shock.
• The receptor's structure suggests a mechanism of signal transduction involving GTP-binding proteins.