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Effects of hepoxilin A3 and its analogues on the function of human eosiophil and basophil granulocytes
- Abstract
- Hepoxilins are formed from arachidonic acid via 12-lipoxygenase pathway. Three isoforms of 12-lipoxygenase have been described and are widely expressed in immune cells an tissue, such as skin and lung. With respect to its diverse biological actions hepoxilin A3 is considered as the most relevant of this class of eicosanoids. In vivo and in vitro studies suggest that hepoxilin A3 has both pro-inflammatory and anti-inflammatory actions, and might play a role in the resolution phase of inflammatory conditions. Although hepoxilins are likely to be abundant at sites of allergic reactions, such as lung and skin, no data is available to-date on the effect of hepoxilins on eosinophil and basophil function, which are important effector cells involved in early- and late-phase allergic responses. In preliminary experiments we observed that hepoxilin A3 is a potent and highly effective inhibitor of eosinophil chemotaxis in vitro. Therefore, the proposed studies aim at further clarifying the actions of hepoxilin A3 on eosinophil and basophil function, including chemotaxis to a wide range of chemoattratants, degranulation, respiratory burst, cell survival and mobilisation of eosinophils from the bone marrow. In addition to their cytotoxic products eosinophils are also an important source of inflammatory mediators, such as leukotrienes and cytokienes.
We expect this study to provide better insights into the role of 12-lipogenases in general, and hepoxilins in particular, in regulating eosinophil and basophil function in order to predict the biological and pharmacological relevance hepoxilins in allergic disease. The study might hence yield novel regimes for the treatment of allergic diseases.
- Project Leader:
- Schuligoi Rufina
- Heinemann Akos
- Peskar Bernhard
- Duration:
- 01.11.2004-30.04.2006
- Programme:
- Jubiläumsfonds (ÖNB)
- Type of Research
- applied research
- Staff
- Schuligoi, Rufina, Project Leader
- Heinemann, Akos, Project Leader
- Peskar, Bernhard, Project Leader
- MUG Research Units
- Division of Pharmacology