Showing papers by "Ronit Sagi-Eisenberg published in 2015"

The search for mast cell and basophil models – are we getting closer to pathophysiological relevance?

Abstract: Mast cells (MC) and basophils (BAS) have long been recognized for their detrimental role in the elicitation of allergic diseases. In recent years, scientific results revealed both cell types as versatile effector cells that exhibit far more complex functions beyond their role in allergy. MC and BAS have been shown to be critically involved in various innate and adaptive immune responses and, thereby, providing beneficial host protecting immunity. In contrast, they also contribute to the development and maintenance of several chronic inflammatory diseases that, even at the present time, lack sufficient treatment options. The diversity of important MC and BAS functions places these cell types into promising therapeutic targets. COST is an intergovernmental framework for European Cooperation in Science and Technology, allowing the coordination of nationally funded research on a European level. The COST Action ‘BM1007 Mast Cells and Basophils – Targets for Innovative Therapies’ is a network of European experts to foster a multidisciplinary approach for the identification, characterization and development of such targets and their translation into novel therapeutic strategies. In addition, the Action provides a platform for young researchers to gain up-to-date insights into the field. The 2nd COST Action BM1007 Training School was held in Jerusalem, Israel, in January 2014 as part of the COST Action working group activities to study the physiological and pathophysiological importance of MC and BAS in health and disease. Thirty-four students from 12 countries across Europe participated in two full and intensive days of training and discussion about the pathophysiological relevance, benefits and limitations of in vitro and in vivo models currently available for MC and BAS research. This report summarizes and concludes on its outcomes.

Investigating mast cell secretory granules; from biosynthesis to exocytosis.

Abstract: Mast Cells (MC) are secretory cells of the immune system that accomplish their physiological and pathological functions by releasing pre-formed and newly synthesized allergic, inflammatory and immunoregulatory mediators. MCs’ mediators affect multiple tissues and organs culminating in allergic and immune responses. The synthesis, storage and release of the MC mediators are highly regulated. The pre-formed mediators are packed in cytoplasmic secretory granules (SG) that fuse with the plasma membrane and release their content by regulated exocytosis. We present a protocol, based on the co-expression of a gene of interest with a reporter gene that is targeted to the SGs and is released in a regulated fashion alongside the endogenous SG mediators. The protocol enables high resolution four dimensional confocal analyses of the MC SGs and monitoring their timeline from biogenesis to triggered exocytosis. Thus, using this protocol for screening genes of interest for their phenotypic and functional impact allows deciphering the molecular mechanisms that govern the biogenesis and exocytosis of the MC SGs and identifying the regulators involved. Thereby, further insights into the cellular mechanisms that account for MCs function in health and disease should be provided.