Complement C5a receptor antagonism by protamine and poly-L-Arg on human leukocytes

Area of Science:

• Immunology
• Pharmacology
• Cell Biology

Background:

• Leukocyte activation by complement component 5a (C5a) is a key inflammatory pathway.
• Understanding C5a receptor interactions is crucial for modulating immune responses.

Purpose of the Study:

• To investigate the inhibitory effects of arginine-rich polycations, protamine and poly-L-Arg, on C5a-induced leukocyte activation.
• To elucidate the mechanism of action of these polycations on C5a receptors.

Main Methods:

• Dose-response studies of protamine and poly-L-Arg on human basophils and neutrophils.
• Assays for histamine release, chemiluminescence, and beta-glucuronidase release.
• Evaluation of the reversibility of polycation inhibition.

Main Results:

• Protamine selectively and dose-dependently inhibited C5a-induced histamine release from basophils and chemiluminescence/enzyme release from neutrophils.
• Protamine and poly-L-Arg demonstrated competitive antagonism of C5a receptors on neutrophils, with reversible inhibitory capacity.
• Poly-L-Arg alone induced degranulation in both cell types.

Conclusions:

• Arginine-rich polycations, protamine and poly-L-Arg, act as competitive antagonists of C5a receptors on human neutrophils.
• Protamine also inhibits C5a receptors on basophils.
• The findings suggest a reversible binding mechanism involving polycation interaction with negatively charged C5a receptor sites.