Mechanisms of asthma and allergic inflammationMast cells: Ontogeny, homing, and recruitment of a unique innate effector cell
Section snippets
MC subsets and heterogeneity
MCs were first recognized in the tissues of various organs on the basis of the unique metachromatic staining characteristics of their secretory granules.5 Subsequent studies discriminated 2 distinct MC subpopulations in the rodent intestine.6, 7 One MC population possesses safranin-positive granules and resides in the submucosal connective tissues and was termed connective tissue MCs (CTMCs). The granules of CTMCs stained even after formalin fixation of the tissues. The second MC population
Intestinal homing
The remarkable abundance of committed MCPs in the small intestine provides an opportunity to understand some of the constitutive homing mechanisms of this lineage. Clonogenic MCP enumeration assays revealed that C57BL/6 mice bearing a targeted deletion of β7 integrins completely lacked intestinal MCPs at baseline.25 These mice also lacked mature MCs in both the submucosal and mucosal compartments, indicating that the missing MCP population was essential for the development of both anatomic
Summary
The involvement of MCs in multiple disease processes, as well as their importance as a therapeutic target in asthma, allergy, and potentially other inflammatory diseases, highlights a need to understand the mechanisms for their development and widespread distribution. Although studies done in the mouse can be extended to the human system only with caution, the unique lineage pathway of MC development, with the terminal stages taking place in peripheral tissues, presents a challenge for
References (37)
- et al.
Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13)
Blood
(1999) - et al.
Identification and characterization of undifferentiated mast cells in mouse bone marrow
Blood
(2005) - et al.
In vivo exit of c-kit+/CD49dhi/{beta}7+ mucosal mast cell precursors from the bone marrow following infection with the intestinal nematode Trichinella spiralis
Blood
(2004) - et al.
Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2
Blood
(2005) - et al.
Chemokine-cytokine cross-talk. The ELR+ CXC chemokine LIX (CXCL5) amplifies a proinflammatory cytokine response via a phosphatidylinositol 3-kinase-NF-kappa B pathway
J Biol Chem
(2003) - et al.
Impaired kit- but not FcepsilonRI-initiated mast cell activation in the absence of phosphoinositide 3-kinase p85alpha gene products
J Biol Chem
(2000) Mast cells: beyond IgE
J Allergy Clin Immunol
(2003)- et al.
Mast cells in autoimmune disease
Nature
(2002) - et al.
Development of mast cells from grafted bone marrow cells in irradiated mice
Nature
(1977) - et al.
Frequency of mast cell precursors in normal tissues determined by an in vitro assay: antigen induces parallel increases in the frequency of P cell precursors and mast cells
J Immunol
(1983)
Uber die specifischen granulationen des Blutes
Arch Anat Physiol Lpz
Mast cells in rat gastrointestinal mucosa. 1. Effects of fixation
Acta Pathol Microbiol Scand
Mast cells in rat gastrointestinal mucosa. 2. Dye-binding and metachromatic properties
Acta Pathol Microbiol Scand
Biology of the mast cell
Mast cells that reside at different locations in the jejunum of mice infected with Trichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype
J Cell Biol
Airway mucosal inflammation even in patients with newly diagnosed asthma
Am Rev Respir Dis
Evidence for Th2-type T helper cell control of allergic disease in vivo
Springer Semin Immunopathol
Absence of intestinal mast cell response in congenitally athymic mice during Trichinella spiralis infection
Nature
Cited by (0)
Supported by grants HL 036110, AI 031599, AI 48802, and AI 052353 from the National Institutes of Health.
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.