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Other publication - Peer-reviewed, 2014

Airway mast cells and lymphocytes from horses are sensitive to cell death induced by lysosomal membrane permeabilization

Wernersson, Sara; Riihimäki, Miia; Pejler, Gunnar; Waern, Ida


Mast cells are known for their detrimental effects in allergic disorders and mastocytosis in humans as well as in animals. Regimens that induce apoptosis specifically in mast cells may therefore be used as efficient therapies in both human and veterinary medicine. Earlier studies have demonstrated that murine and human cultured mast cells are highly sensitive to apoptosis induced by the lysosomotropic agent LeuLeuOMe (LLME). The aim of the present study was to examine the effect of LLME on the different native cell populations in horse airways. Bronchoalveolar lavage (BAL) fluid were collected from three horses and differential cell counting demonstrated an average of 77% macrophages, 17% lymphocytes, 3.6% mast cells, 1.6% neutrophils and 0.6% eosinophils. The BAL cells were incubated with an increasing dose of LLME (15, 50 and 100 µM) for up to 48h. The total cell viability was unaffected by 15 µM LLME and was around 30% reduced by higher doses of LLME at 48h incubation. We found a dose dependent effect of LLME on mast cell numbers with an almost complete depletion (96%) of mast cells after 24h incubation with 100 µM LLME. A significant but less dramatic reduction (up to 45%) was seen in the lymphocyte population whereas macrophages and neutrophils were essentially resistant to LLME-induced cell death. The appearance of apoptotic bodies in dying cells after LLME-treatment suggested a mechanism involving apoptosis rather than necrosis. In summary, we here show that equine airway mast cells are highly sensitive, and lymphocytes are moderately sensitive, to cell death induced by LLME. Possibly, lysosomotropic agents could be of therapeutic value to treat disorders involving harmful accumulation of mast cells or lymphocytes in the airways.

Published in

Book title: IMCBM 2014 Book of abstracts
Publisher: International Mast Cell and Basophil Meeting