A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study

Abstract

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.

Figure 1

Microscopic caecal mucosal architecture (×400) showing mast cell staining pink with chloracaetate esterase, the number of intact mast cells was averaged over at least 50 caecal mucosal crypts.

Figure 2

The relationship between mast cell degranulation (a) and the appearance of macroscopic (b) and microscopic (c) caecal vasculitis in HgCl₂-challenged animals in experiment 1; all figures represent the median scores for individual time points.

Figure 3

Macroscopic (a) and microscopic (b) caecal vasculitis scores seen 48 h after a second challenge in experiment 2.

Figure 4

Macroscopic (a) and microscopic (b) caecal vasculitis scores seen 48 h after a second challenge in experiment 4.

Figure 5

The correlation between intact mast cells remaining per mucosal crypt and the severity of macroscopic (a) and microscopic (b) caecal vasculitis in experiment 4. Symbols reflect type of challenge given to animal: ○, saline/–, ▵:HgCl₂/–, •:saline/HgCl₂, ▵:HgCl₂/HgCl₂.

Figure 6

Macroscopic caecal vasculitis scores in recipient animals in experiment 5. Animals were scored at 48 h after HgCl₂ challenge with recipients rested for 24 h (a) or 7 days (b) following transfer of donor cells prior to HgCl₂ challenge.