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Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Characterization and modulation of canine mast cell derived eicosanoids
Tzu-Yin Lin1, Cheryl A London1
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 454 VMAB, 1925 Coffey Road, Columbus, OH 43210, USA.
Veterinary Immunology and Immunopathology
|December 29, 2009
Summary
Canine mast cells produce various inflammatory mediators, including prostaglandins and leukotrienes. A pan COX/LOX inhibitor, tepoxilan, effectively reduced eicosanoid production, showing potential for treating canine inflammatory disorders.
Area of Science:
- Veterinary Immunology
- Pharmacology
Background:
- Mast cells are crucial in immune responses and inflammatory conditions like allergies and neoplasia.
- Eicosanoids (prostaglandins, leukotrienes) are key mediators produced by mast cells, but their spectrum in canine mast cells is poorly understood.
- Modulating mast cell-derived eicosanoids offers potential therapeutic strategies for canine autoimmune and inflammatory disorders.
Purpose of the Study:
- To identify the range of eicosanoids produced by normal canine mast cells.
- To assess the impact of cytokines and non-steroidal anti-inflammatory drugs (NSAIDs) on canine mast cell eicosanoid production and release.
Main Methods:
- Canine bone marrow-derived cultured mast cells (cBMCMCs) were utilized.
- Expression of cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase (5-LOX) was analyzed.
- Eicosanoid production (PGD2, PGE2, LTB4, LTC4) was measured after activation and treatment with various NSAIDs and inhibitors.
Main Results:
- Canine mast cells express COX-1, COX-2, and 5-LOX, producing PGD2, PGE2, LTB4, and LTC4.
- Selective COX-2 inhibitors (carprofen, deracoxib) reduced PGD2 and PGE2 but had minimal effect on LTB4/LTC4.
- A pan COX/LOX inhibitor (tepoxilan) significantly reduced all measured eicosanoids, while a LOX inhibitor (NDGA) inhibited LTB4/LTC4 and degranulation.
Conclusions:
- Canine mast cells produce a diverse array of eicosanoids, comparable to other species.
- Tepoxilan demonstrated the most potent inhibition of eicosanoid production, suggesting its utility in managing mast cell-mediated inflammatory conditions in dogs.
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