1. Department of Medicine I, Division of Hematology & Hemostaseology and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Austria.
2. Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, MI, USA.
3. Division of Allergy, Department of Dermatology, University of Basel, Basel, Switzerland.
4. Department of Medicine Solna & Mastocytosis Centre, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
5. Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.
6. Imagine Institute Université Paris Descartes, Sorbonne, Paris Cité, Centre national de référence des mastocytoses, Paris, France.
7. Institute of Pathology, Paracelsus Medical University Salzburg, Austria.
8. Servicio Central de Citometria (NUCLEUS), Centro de Investigacion del Cancer (IBMCC; CSIC/USAL and CIBERONC) and Department of Medicine, University of Salamanca, Spain.
9. Department of Pathology, University of Utah, Salt Lake City, UT, USA.
10. Department of Hematology, University Medical Center Groningen, University of Groningen, The Netherlands.
11. Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
12. Division of Allergy and Clinical Immunology, University of Salerno, Italy.
13. Department of Dermatology and Allergy Biederstein, Technical University of Munich, Germany.
14. Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA.
15. Wihuri Research Institute, Helsinki, Finland.
16. Department of Companion Animals and Horses, Small Animal Clinic, Internal Medicine, University of Veterinary Medicine Vienna, Austria.
17. Institute of Pathology, Ludwig Maximilian University, Munich, Germany.
18. INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France.
19. Department of Internal Medicine, Division of Rheumatology, Allergy & Immunology, Virginia Commonwealth University, Richmond, VA, USA.
20. Division of Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.
21. Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD, USA.
22. Departments of Pathology and of Microbiology and Immunology, and the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, USA.
*This paper, reflecting both the more recent developments in the field and the presentations and discussions at a meeting held in 2015 to mark the 100th Anniversary of the death of Paul Ehrlich, is dedicated to the pioneering work and scientific achievements of this remarkable scientist.
The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years. MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs. In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings. The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells. The clinical consequences of the expansion and/or activation of MCs are best established in mastocytosis and in allergic inflammation. However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes. In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease. We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs.
Keywords: histamine, IgE receptor, KIT, mast cell activation, mastocytosis, tryptase