Complement-induced histamine release from human basophils. III. Effect of pharmacologic agents

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• Human serum activated with zymosan generates C5a, a factor that releases histamine from basophils.
• Previous evidence suggests C5a-induced histamine release mechanisms differ from IgE-mediated reactions.
• Understanding these distinct pathways is crucial for targeted therapeutic interventions.

Purpose of the Study:

• To investigate the effects of various pharmacologic agents on serum-induced histamine release.
• To compare the mechanisms of C5a-mediated histamine release with IgE-mediated histamine release.
• To elucidate the cellular pathways involved in C5a-induced histamine release.

Main Methods:

• Human basophils were incubated with zymosan-activated serum.
• The effects of deuterium oxide (D2O), cytochalasin B, colchicine, dibutyryl cyclic AMP, aminophylline, isoproterenol, cholera toxin, chlorphenesin, diethylcarbamazine, and 2-deoxy-D-glucose on histamine release were assessed.
• Experiments were conducted at varying temperatures (25 and 32 degrees C).

Main Results:

• Deuterium oxide (D2O) inhibited serum-induced histamine release in a concentration-dependent manner at 25 and 32 degrees C.
• Cytochalasin B significantly enhanced serum-induced histamine release.
• Several agents known to inhibit IgE-mediated release, including colchicine, dibutyryl cyclic AMP, and aminophylline, also inhibited serum-induced release at 25 degrees C.

Conclusions:

• Serum-induced histamine release is modulated by intracellular cyclic AMP, requires energy, and is enhanced by microfilament disruption.
• The lack of D2O effect suggests microtubular stabilization is not required for C5a-mediated release.
• IgE- and C5a-mediated histamine release pathways diverge at a late stage.