Περίληψη:
Background: Mast cells are involved in allergy and inflammation by the
secretion of multiple mediators, including histamine, cytokines, and
platelet-activating factor (PAF), in response to different triggers,
including emotional stress. PAF has been associated with allergic
inflammation, but there are no clinically available PAF inhibitors.
Objective: To investigate whether PAF could stimulate human mast cell
mediator release and whether rupatadine (RUP), a dual histamine-1 and
PAF receptor antagonist, could inhibit the effect of PAF on human mast
cells.
Methods: Laboratory of allergic diseases 2 cultured mast cells were
stimulated with PAF (0.001, 0.01, and 0.1 mu mol/L) and substance P (1
mu mol/L) with or without pretreatment with RUP (2.5 and 25 mu mol/L),
which was added 10 minutes before stimulation. Release of
beta-hexosaminidase was measured in supernatant fluid by
spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis
factor were measured by enzyme-linked immunosorbent assay.
Results: PAF stimulated a statistically significant release of
histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 mu mol/L)
that was comparable to that stimulated by substance P. Pretreatment with
RUP (25 mu mol/L) for 10 minutes inhibited this effect. In contrast,
pretreatment of laboratory of allergic diseases 2 cells with
diphenhydramine (25 mu mol/L) did not inhibit mediator release,
suggesting that the effect of RUP was not due to its antihistaminic
effect.
Conclusion: PAF stimulates human mast cell release of proinflammatory
mediators that is inhibited by RUP. This action endows RUP with
additional properties in treating allergic inflammation. (C) 2013
American College of Allergy, Asthma & Immunology. Published by Elsevier
Inc. All rights reserved.
Συγγραφείς:
Alevizos, Michail
Karagkouni, Anna
Vasiadi, Magdalini and
Sismanopoulos, Nikolaos
Makris, Michael
Kalogeromitros,
Dimitrios
Theoharides, Theoharis C.
