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In their letter, Hyland et al report differences between data they obtained on mast cell phenotype and the role in visceral hypersensitivity to colorectal distension in adult rats previously submitted to maternal separation, and those we obtained using the same experimental protocol.1 They confirm the existence of colonic mast cell hyperplasia in maternally deprived rats, but they found it localised in the submucosa, while in our paper it was clearly localised in the mucosa. It has been shown that protease phenotype of mast cells and their locations in epithelium, lamina propria and submucosa may vary according to the different phases of an acute inflammation.2 Since maternal deprivation is known to induce a moderate colonic inflammation in adults, we can speculate that the inflammatory state was different in our rats and those of Hyland et al, because of differences of strains or differences in rearing conditions.
According to the characteristics of mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs) provided by Metcalfe et al,3 mast cells described in our paper are clearly MMCs on the basis of size and content of rat mast cell protease II (RMCPII). Hyland et al propose that the mast cells they described are CTMCs, since it has been suggested in one paper that some intestinal CTMCs may be RMCPII positive. We did not find any clear evidence of this statement in the paper they cite, and we agree with the conclusion that the “exact source, MMC or CTMC, is unclear”.
Our paper indicates that the amount of RMCPII released by colonic tissue in basal conditions, or under stimulation by substance P or a calcium ionophore, is increased in maternally deprived rats. Interestingly, Hyland et al confirm this increased release using another stimulating agent. We have also shown in another paper4 that the hypersensitivity to colorectal distension, characterising maternally deprived rats, was abolished by the mast cell stabiliser doxantrazole. Hyland et al do not confirm this result. They verified that doxantrazole treatment was effective, since it reduced the RMCPII release after anti-IgE stimulation. In our study, we used a different protocol (two injections at the dose of 5 mg/kg at 6 h and 1 h before colorectal distension, instead of a unique injection at the same dose 30 min before distension). These differences in results can be explained by the fact that, despite the decreased release of RMCPII after doxantrazole, there is a residual release of mast cell mediators in sufficient amount to induce hypersensitivity.
Finally, despite some differences in the results, very likely due to subtle differences in experimental protocols, the data obtained by Hyland et al confirm that stress associated with maternal deprivation in the early days of life induces long-term sensitisation of the colonic immune system.
Competing interests: None.
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