Mast Cells and Basophils - No 271: Development, Activation and Roles in Allergic/Autoimmune Disease / Edition 1

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Delve into the latest research on mast cells and basophils and thier significance vis-a-vis multiple sclerosis, disbetes, HIV-1 infection, and other allergic and autoimmune diseases. This exciting new book covers recent advances relatiing to the factors and mechanisms that regulate the growth, differentiation, and function of mast cells and basophils. World leaders in the field describe new technologies used to study these cells. They aslo show how the basic scientific findings can be integrated into possible therapeutic applications. Some of the discussions examine the part played by mast cells in allergic inflammation and the effect that the stabilization of these cells has in novel therapies. There is also coverage of mastocytosis and the underlying mutations.

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Editorial Reviews

Doody's Review Service
Reviewer: Mark C. Glaum, MD, PhD (University of South Florida College of Medicine)
Description: This book reviews the most recent research on the role of mast cells and basophils in allergic and autoimmune diseases. Topic reviews are followed by discussion among international experts in mast cell and basophil biology.
Purpose: The purpose is to provide basic researchers or clinicians with a concise, timely review of the factors and mechanisms regulating the growth, differentiation and function of mast cells and basophils. This is en ever-evolving field, therefore periodic updates in this area are needed. Emphasis is placed on new technologies used to study mast cell and basophil function, and attention is focused on how basic scientific observations can be translated into possible therapeutic applications.
Audience: Discussion is targeted to researchers and clinicians who have an interest in mast cell and basophil biology. Specialists most likely to use this book include allergists, clinical immunologists, rheumatologists, and dermatologists. Clinical and research fellows will also find it to be an excellent review of basic mechanisms of mast cell and basophil growth, differentiation, and activation.
Features: Each chapter is presented in the format of a topic review, which is followed by specific discussion of the topic among seminar panelists. A general discussion of the presented material is included every 3 to 5 chapters. The topics include: development of mast cells and basophils, IgE-mediated activation of mast cells and basophils, mechanisms of exocytosis, non-IgE-mediated activation and modulation of mast cells and basophils, description of mediators including those that are lipid-derived, proteases, proteoglycans and cytokines. Each chapter is well referenced and participant and subject indexes are included. The compact size of the book makes transport manageable.
Assessment: This is an excellent review of current research in mast cell and basophil biology. The discussion sections provide unique insight from world-recognized experts in the field. This is an excellent resource for clinicians or basic scientists with an interest in mast cells and related diseases.
From the Publisher
"This is an excellent resource for clinicians or basic scientists with an interest in mast cells and related diseases." (Doody's Health Services)
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Product Details

  • ISBN-13: 9780470013120
  • Publisher: Wiley
  • Publication date: 11/29/2005
  • Series: Novartis Foundation Symposia Series, #192
  • Edition number: 1
  • Pages: 274
  • Product dimensions: 6.20 (w) x 9.13 (h) x 0.72 (d)

Read an Excerpt

Mast Cells and Basophils

John Wiley & Sons

ISBN: 0-470-01312-5

Chapter One

Chair's introduction

Santa Jeremy Ono

University College London, 11-43 Bath Street, London EC1V 9EL, UK

I would like to welcome all of you to this Novartis Foundation Symposium on Mast cells: development, activation and roles in allergic/autoimmune disease. We are fortunate to have assembled a tremendous group of investigators in the field and I am sure that this will result in an intense scientific meeting focusing on the latest basic (primarily molecular) research studies on the mast cell and basophil, and their relation to allergic and autoimmune diseases. The overall goal of this symposium is to advance our knowledge of the roles of these two granulocytes in varied disease settings such as those occurring in allergic inflammation and autoimmune disease.

With its focus on molecular aspects of mast cells and basophils, the meeting is part of a distinguished history of Novartis Foundation symposia in the area of hypersensitivity and autoimmunity. We all recall the first superb symposium chaired by Henry Metzger from the National Institutes of Health and the more recent one on anaphylaxis chaired by Steve Galli from Stanford. Importantly, this meeting will be quite distinct from the latter: while there is some overlap (since IgE signalling is key to anaphylaxis), the topics covered in that meeting were much broader, with a focus on the disease. This symposium, in contrast, focuses on mast cell development, activation and communications with other cells at the molecular level.

The three specific goals of the symposium are:

(1) To present recent advances relating to the factors and mechanisms that regulate the growth, differentiation, and function of mast cells and basophils.

(2) To discuss new technological advances that directly impact studies on mast cells and basophils.

(3) To integrate the basic science findings on mast cells and basophils into the framework of therapeutic potential and treatment of diseases such as allergic inflammation and autoimmune disease which are mediated, in part, by these granulocytes.

The meeting will focus on contemporary issues of mast cell/basophil research as they relate to the pathogenesis of allergic and autoimmune diseases. The topics will include: (1) the development of mast cells and basophils; (2) early and late events in IgE/antigen activation of mast cells and basophils; (3) mechanisms of exocytosis; (4) non-IgE mediated activation of mast cells and basophils, as well as those surface receptors that dampen activation responses; (5) protease, proteoglycan, lipid, and cytokine mediators released from activated mast cells and basophils; and (6) bilateral interactions of mast cells with other cell types.

The presentations in the area of mast cell development will examine some of the key intracellular factors that control mast cell development in humans and mice. Analysis of gene expression in mast cells that have been activated by different mechanisms is yielding important new information on genes and their products that are involved in mast cell development and activation. Additional information on embryonic stem cells that differentiate into mast cells is also emerging. Specifically, in vitro differentiated mast cells in adoptive transfer approaches address issues concerning mast cell development, signal transduction and function in vivo.

Presentations on early events in FceRI-mediated activation of mast cells and basophils will focus on the molecular basis of activation of these cells. They will include models stemming from biophysical and crystallographic studies of the high-affinity IgE receptor FceRI and its interactions with IgE. Other topics will include major molecules and their interactions that govern the signalling pathways stimulated by FceRI in mast cells. The task ahead is to determine the critical factors that regulate the strength and persistence of signalling. Data on the relationship between ligand valency, affinity, and the kinetics of binding to a variety of cellular responses will be presented. The value of a quantitative model of the signalling cascades initiated by the aggregation of FceRI, as well as some of the difficulties encountered in the development and use of such a model, should also be discussed. The interactions between multivalent antigens and sIgE give rise to a complex distribution of FceRI aggregates on the surfaces of mast cells and basophils. Quantifying the clustering of FceRI in 'real time' is yielding new insight into the biophysics of IgE-mediated mast cell activation. Other discussions might include the roles of detergent- insoluble membrane microdomains and lipid rafts. This will also include discussion on the facilitation of tyrosine phosphorylation of cross-linked receptors by Lyn in a process that is regulated, in part, by the actin cytoskeleton.

Presentations on signalling complexes and downstream signalling in FceRI-mediated activation of mast cells and basophils will explore some of the downstream events that occur prior to exocytosis of the cell's secretory granules. Discussions will likely focus on IgE receptor-activated macromolecular signalling complexes in mast cells, as well as the importance of the constituent molecules in mast cell degranulation and cytokine production.

There will also be presentations and discussion on the exocytosis of mediators from activated mast cells and basophils. They will include talks on cytoskeletal rearrangements required for degranulation of these effector cells, and the link between membrane activation events and these processes.

We also anticipate active debate on inhibition of FceRI-mediated responses and non-IgE mechanisms of mast cell and basophil activation focusing on the signalling pathways controlled by cytokines, chemokines and their receptors. It is now apparent that FceRI-mediated activation of mast cells and basophils can be either stimulated or counteracted by other receptors on the surfaces of these cells. It is also apparent that certain populations of mast cells and basophils can be activated by surface receptors other than FceRI. Of particular interest will be the role chemokine receptors play in mast cell development, mast cell progenitor homing, and mast cell activation.

The symposium will end with a discussion of the interaction of mast cells and other cell types, and the role of the mast cells/basophils in disease. Some of the discussions will naturally focus on the role of mast cells in allergic inflammation, and the role of stabilization of these cells in novel therapies. There will also be discussions on mastocytosis and the mutations that give rise to this phenotype. In addition, significant attention will be placed on recent data suggesting a role for mast cells in multiple sclerosis, diabetes and HIV-1 infection. Indeed recent studies have implicated mast cells in processes that control the onset and severity of experimental allergic encephalomyelitis and insulin-dependent diabetes (IDDM) in mice. The strategic location of mast cells in the central nervous system (in multiple sclerosis) and in the pancreas (in IDDM) as well as their ability to express a variety of cytokines and other inflammatory mediators raises the possibility that mast cells either directly initiate the inflammatory responses or act to modulate the character of the T cell response in this disease.

In conclusion, I anticipate that this symposium (and the book that results from the presentations and discussions) will take its place alongside the previous Novartis Foundation symposia chronicling the study of mast cells and basophils in health and disease. Let the work and the discussions help form the salient future questions, and draw in young scientists who will carry forward this field of research.


Excerpted from Mast Cells and Basophils Excerpted by permission.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

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Table of Contents

Symposium on Mast cells and basophils: development, activation and roles in allergic/autoimmune disease, held at the Novartis Foundation, London, 16–18 November 2004
Editors: Derek J. Chadwick (Organizer) and Jamie Goode
This symposium was based on a proposal made by Santa Jeremy Ono.

Santa Jeremy Ono: Chair’s Introduction.

Yukihiko Kitamura MITF and SgIGSF: an essential transcription factor and its target adhesion molecule for development and survival of mast cells

Paul J. Bryce, Mendy L. Miller, Ichiro Miyajima, Mindy Tsai, Stephen J. Galli and Hans C. Oettgen: Immune sensitization in the skin is enhanced by antigen-independent effects of IgE on mast cells

Yasuko Furumoto, Gregorio Gomez, Claudia Gonzalez-Espinosa, Martina Kovarova, Sandra Odom, John J. Ryan and Juan Rivera: The role of Src family kinases in mast cell effector function

Richard L. Stevens, Nasa Morokawa, Jing Wang and Steven A. Krilis: RasGRP4 in mast-cell signalling and disease susceptibility

J. Abramson, E. A. Barbu and I. Pecht: Regulation of mast cell secretory response to the type I Fce receptor: inhibitory elements and desensitization

General discussion I.

Toshiaki Kawakami, Jiro Kitaura, Wenbin Xiao and Yuko Kawakami: IgE regulation of mast cell survival and function

See-Ying Tam, Janet Kalesnikoff, Susumu Nakae, Mindy Tsai and Stephen J. Galli: RabGEF1, a negative regulator of Ras signalling, mast cell activation and skin inflammation

Masako Toda, Takao Nakamura, Masaharu Ohbayashi, Yoshifumi Ikeda, Maria Dawson, Ricardo Micheler Richardson, Andrew Alban, Benjamin Leed, Dai Miyazaki and Santa Jeremy Ono: Role of CC chemokines and their receptors in multiple aspects of mast cell biology: comparative protein profiling of FceRI- and/or CCR1-engaged mast cells using protein chip technology

General discussion II.

Shigeo Koyasu, Akiko Minowa, Yasuo Terauchi, Takashi Kadowaki and Satoshi Matsuda: The role of phosphoinositide-3-kinase in mast cell homing to the gastrointestinal tract

K. Frank Austen: The mast cell and the cysteinyl leukotrienes

Silvia Monticelli, K. Mark Ansel, Dong U. Lee and Anjana Rao: Regulation of gene expression in mast cells: micro-RNA expression and chromatin structural analysis of cytokine genes

Cellina Cohen-Saidon and Ehud Razin: The involvement of Bcl-2 in mast cell apoptosis

General discussion III.

P. A. Nigrovic and D. M. Lee: Mast cells in autoantibody responses and arthritis

Greg D. Gregory, Allison Bickford, Michaela Robbie-Ryan, Mindy Tanzola and Melissa A. Brown: MASTering the immune response: mast cells in autoimmunity

Dean D. Metcalfe: Mastocytosis

Index of Contributors.

Subject Index.

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