Mast cells, histamine and the pathogenesis of intestinal damage in experimental Trypanosoma brucei brucei infections

Intestinal damage with increased permeability is a prominent feature of experimental African trypanosomiasis. The possible involvement of mast cells and histamine in the altered gut integrity was investigated, at the level of the jejunum, in BALB/c mice infected with Trypanosoma brucei brucei. Mast cells were studied by selective staining of granule content with Alcian Blue/Safranin and quantitative histology, and histamine concentrations were determined by a fluorimetric method. Mast-cell activation, shown by a marked reduction in the numbers of positive-staining cells seen per villous section, was prominent on days 7 and 14 post-infection (there was, for example, a reduction to 36% of the control value by day 14; P = 0.0001). By day 2 1, however, there were 131% more staining cells per villous section in the infected mice than in the uninfected controls (P = 0.003). Histamine levels in homogenates of the jejunal mucosae of the infected mice were found to be significantly elevated at each time-point. The maximum increase was observed on day 14, when the numbers of granulated mast cells were at their lowest, with mean (S.E.) concentrations of 6.744 (0.890) ng/mg tissue for the infected mice and 2.813 (0.321) ng/mg for the uninfected controls (P = 0.0008). The jejunal mucosa suffered progressive morphological damage during the infection, with oedema of the lamina propria and villi and disruption of the endothelium. These results indicate that mast cells are involved with the intestinal pathology that develops during experimental African trypanosomiasis.