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Secretion of inflammatory mediators from eosinophils and their tissue residing cell-free granules: mechanisms and implications in inflammation

Objective

Eosinophils, both as end-stage effector cells and as Th2-immunomodulators, have the capacity to secrete varied inflammatory mediators, such as, cytokines and enzymes that are stored in their cytoplasmic secretory granules. Among them are the cationic proteins: major basic protein, eosinophil peroxidase, and the eosinophil RNases. In the last decade several studies, both in vitro and in vivo, have revealed a pivotal role for eosinophils and their granule content in immunomodulation, host defence and in pathology of eosinophil-associated diseases, such as allergy and asthma. Eosinophil secretion of granules content (e.g. degranulation) and the deposit of its cationic proteins are associated with a range of inflammatory disorders. Degranulation typically by means of piecemeal degranulation, is a controlled and selective process. In addition, at sites of inflammation, cytolysed eosinophils release cell-free granules, that reside in inflamed tissue.
Recently, studies by me and my colleagues have revealed that beside secretion from intact cells, cell-free granules released from human and mouse eosinophils during lysis have the ability to secrete their content in response to cytokine stimulation in a cell free context. However, the mechanisms of these two methods of secretion and the key factors that participate in the degranulation process in intact eosinophils and especially in cell-free granules are poorly understood.
The current proposal aims to explore the physiological functions of the newly discovered mode of secretion from eosinophil-derived cell free granules in allergic airway inflammation and the mechanisms by which integrins cooperate with elements of the cytoskeleton machinery in regulating chemokine-mediated degranulation in eosinophils. These studies will enhance our understanding of eosinophil degranulation, on the molecular and pathopysiological levels, and will provide potential targets for new directed therapies to treat eosinophil-associated diseases.

Field of science

  • /medical and health sciences/basic medicine/pathology
  • /medical and health sciences/clinical medicine/pneumology/asthma
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/clinical medicine/allergology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP7-PEOPLE-2013-CIG
See other projects for this call

Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

THE HEBREW UNIVERSITY OF JERUSALEM
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Hani Ben Yehuda (Ms.)

Participants (1)

UNIVERSITY OF HAIFA

Participation ended

Israel
Address
Abba Khushy Blvd Mount Carmel
31905 Haifa
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tsvia Beker (Mrs)