Hyperosmolar triggering of histamine release from human basophils

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• Idiopathic reactions to hyperosmolar solutions, such as radiocontrast dyes, are a significant cause of mortality.
• These reactions share similarities with mediator release during allergen-induced anaphylaxis.

Purpose of the Study:

• To investigate the direct effect of hyperosmolarity on human basophils.
• To elucidate the mechanism of nonimmunologic histamine release induced by hyperosmolar stimuli, specifically mannitol.

Main Methods:

• In vitro histamine release assay using human basophils stimulated with hyperosmolar solutions (0.2-0.7 M mannitol).
• Assessment of cytotoxicity using electron microscopy and varying temperature conditions (4°C vs. 37°C).
• Comparative analysis with antigen-induced histamine release, including drug inhibition studies (p-bromophenacyl bromide, eicosa-5,8,11,14-tetraynoic acid) and modulation by deuterium oxide (D(2)O).

Main Results:

• Hyperosmolar solutions, including mannitol, induced histamine release from human basophils.
• The release was non-cytotoxic, evidenced by stimulus inhibition at 37°C, lack of release at 4°C, and intact cell membranes.
• Mannitol-induced release exhibited similarities to antigen-induced release (time-course, drug sensitivity) but differed in its independence from IgE, cyclic AMP, and extracellular calcium, with a distinct temperature optimum of 32°C.

Conclusions:

• Hyperosmolar-induced histamine release from basophils is a non-cytotoxic process distinct from IgE-mediated anaphylaxis.
• This mechanism may contribute to idiopathic reactions observed after the infusion of hyperosmolar agents in clinical settings.