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Research article2017Peer reviewedOpen access

Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents

Wernersson, S.; Riihimaki, M.; Pejler, G.; Waern, I.


Mast cells are known for their detrimental effects in various inflammatory conditions. Regimens that induce selective mast cell apoptosis may therefore be of therapeutic significance. Earlier studies have demonstrated that murine-and human-cultured mast cells are highly sensitive to apoptosis induced by the lysosomotropic agent LeuLeuOMe (LLME). However, the efficacy of lysosomotropic agents for inducing apoptosis of in vivo-derived airway mast cells and the impact on mast cells in other species have not been assessed. Here we addressed whether lysosomotropic agents can induce cell death of equine in vivo-derived mast cells. Bronchoalveolar lavage (BAL) fluids from horses were incubated with LLME at 15-100 lM for up to 48 h. The overall cell viability was unaffected by 15 lM LLME up to 48 h, whereas a relatively modest drop in total cell counts (similar to 30%) was seen at the highest LLME dose used. In contrast to the relatively low effect on total cell counts, LLME efficiently and dose dependently reduced the number of mast cells in BAL fluids, with an almost complete depletion (96%) of mast cells after 24 h of incubation with 100 lM LLME. A significant but less dramatic reduction (up to similar to 45%) of lymphocytes was also seen, whereas macrophages and neutrophils were essentially resistant. The appearance of apoptotic bodies suggested a mechanism involving apoptosis rather than necrosis. These findings suggest that equine airway mast cells are highly sensitive to lysosomotropic agents. Possibly, lysosomotropic agents could be of therapeutic value to treat disorders involving harmful accumulation of mast cells in the airways.

Published in

Scandinavian Journal of Immunology
2017, Volume: 85, number: 1, pages: 30-34