Mast cell tumors (MCTs) are the most common cutaneous neoplasm of dogs and third most common intestinal tumor in cats, with a 20% incidence worldwide. Mast cell granules contain pro-inflammatory mediators and vasoactive amines, and potential sequela of mast cell degranulation include life-threatening anaphylaxis and gastrointestinal (GI) ulceration. Patients with MCTs are treated with acid suppressants, including histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), to prevent GI ulceration. Acid suppressants have pH independent effects, including alteration of leukocyte cytokine production, modulation of cell number and function, and changes in mast cell degranulation ability. Mast cell granules require an acidic pH and contain a vacuolar-type ATPase to achieve acidity. This vacuolar ATPase is related to the H+ / K+ ATPase in gastric parietal cells, thus, PPIs may impact MCT function and survival. The effect of acid suppressants, most notably PPIs, on mast cells has not been fully explored.
Using a previously validated in vitro rat mast cell line, RBL-2H3, and mouse bone marrow derived mast cells (BMMCs), our central objectives were to evaluate the effect of H2RA (famotidine) and PPI (esomeprazole) treatment on mast cell degranulation, granule morphology, and cell death. Mast cell degranulation and cell death were assessed using beta-hexosaminidase and flow cytometric assays, respectively. Changes to granule morphology were evaluated via light and ultrastructural microscopy.
Degranulation percentage of RBL-2H3 cells was significantly increased when treated with esomeprazole (P < 0.05; One-way ANOVA with Holm-Sidak post hoc) but not with famotidine or vehicle treatments. Structural changes were observed with both acid suppressants but were more pronounced with esomeprazole.
Acid suppressant treatment altered mast cell degranulation, viability, and structural morphology in vitro, with PPIs having more pronounced effects. Ongoing work will assess the effects of acid suppressant therapy on mast cell tumors in dogs and cats.
Medical Resident (Small Animal Internal Medicine)
University of Tennessee College of Veterinary Medicine
Thursday, June 14
1:30 PM – 1:45 PM
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