Source: Annual Congress 2001 - Molecular and cellular pathology of asthma
Disease area: Airway diseases

Abstract

Background: Allergen-specific CD4+ T cells represent the main cellular population involved in the mucosal allergic immune response. Therefore, the anti-inflammatory action of many anti-asthmatic drugs should be directed principally toward these cells, perhaps favouring their death by apoptosis. The possibility that bloking cysteinyl-leukotriene receptors by in vitro exposure to Montelukast (MNT) could lead to the induction of apoptosis in target cells is currently unknown.
Aim: To verify the pro-apoptotic activity of MNT in different allergen- and non allergen-specific cellular systems.
Methods: Cell sources tested were: 1) peripheral blood T lymphocytes, 2) Jurkat T-cell line and 3) allergen-specific T-cell clones generated from BAL fluid of mite-sensitive asthmatic subjects. The percentage of apoptotic cells was calculated by propidium-iodide staining.
Results: MNT was effective in inducing cell death on anti-CD3-activated peripheral blood T lymphocytes (22 ±] 3%), whereas it was unable to induce apoptosis in resting T cells (8 ±] 2%). Jurkat T-cell line (72 ±] 8%) and allergen-specific pulmonary CD4+ clones (46 ±] 4%) showed an high degree of DNA damage following in vitro exposure to MNT. Dose-response curve showed that the drug concentration able to induce the highest cell death in allergen-specific CD4+ T-cell clones, as well as in Jurkat T-cell line, was 10-6M.
Conclusions: These findings, together with the known pro-apoptotic activity of MNT toward eosinophils, provides an additional mode of action of leukotriene receptor antagonists that may be useful in the treatment of allergic inflammation.

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F. Spinozzi, E. Agea, M. Russano, O. Bistoni, N. Forenza, F. M. De Benedictis (Perugia, Italy). In vitro induction of apoptosis on allergen-specific CD4+ T-cell clones by montelukast. Eur Respir J 2001; 16: Suppl. 31, 3559

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