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Vinen CS, Turner DR, Oliveira DB: A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study. Int J Exp Pathol. 2004 Jun;85(3):165-74. Administration of mercuric chloride (HgCl (2)) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl (2) and then spontaneously resolve. If animals are re-challenged with HgCl (2) 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl (2) and prior to caecal entry of T cells. Previous work suggested this early vasculitis was alpha beta T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl (2) challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl (2). We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl (2) challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury. |
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