Modulation of Phagocytosis in Tetrahymena thermophila by Histamine and the Antihistamine Diphenhydramine

Nikhil Buduma,

Jenny Balabanian,

Pranati Dalvi,

Soo-Khee Chia,

Ashreet Dhaliwal,

Dany Eliya,

John Boothby,

Shannon Bros-Seemann,

Ruthann Kibler,

Sami Khuri,

Sally Veregge

Abstrakt

Histamine is a significant biological compound because of its role in mediating the human allergic and inflammatory pathways. Antihistamines are often administered to control the irritating symptoms of allergic reactions. We evaluated phagocytosis in the protist Tetrahymena thermophila for use in screening for potential therapeutic compounds that mimic histamine and antihistamines. Tetrahymena has been frequently used as an experimental model to study compounds for biological effects or to study biological processes. Histamine and the antihistamine diphenhydramine were administered at concentrations ranging from 10–6 μM to 1000 μM, and the corresponding changes in phagocytosis were detected by flow cytometry. Treatment with histamine had no measurable effect on phagocytosis while diphenhydramine decreased phagocytic levels at concentrations above 50 μM. In a competition experiment between histamine and diphenhydramine, histamine did not reverse the dosage-dependent decrease in phagocytosis elicited by diphenhydramine. BLAST searches revealed no significant homologs of the human histamine receptors in T. thermophila. These results suggest that T. thermophila has a receptor for diphenhydramine that is linked to the phagocytic process, but not a histamine receptor. Further study is necessary to elucidate the nature of this previously uninvestigated receptor. The experimental protocol developed as a part of this study may serve as an inexpensive, high throughput, flow cytometric method to screen natural and synthetic compounds for pharmacologically significant properties.

Słowa kluczowe: Tetrahymena thermophila, phagocytosis, flow cytometry, histamine, diphenhydramine, drug screening

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