Mast cells: Ontogeny, homing, and recruitment of a unique innate effector cell

Mast cells (MCs) are found principally in peripheral tissues yet are of bone marrow origin. Recent studies in mice trace the MC lineage from the common myeloid progenitor through the granulocyte-macrophage progenitor in the bone marrow to a committed MC progenitor (MCP). Additionally, at least in the mouse, a bipotent basophil-MC progenitor has been identified in the spleen, suggesting a physiologic role for this organ in MC development. MCPs are especially abundant in the mouse intestine, likely ensuring the capacity for a rapid expansion of MCs in the intestinal epithelium during the effector response to helminth infection and perhaps providing a pool of committed cells capable of redistribution to other tissues. Migration of MCPs to the intestine is constitutive and controlled by α chemokine receptor 2 and α4β7 integrins expressed on the MCPs, with the latter integrin interacting with endothelial vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule 1. In contrast, normal mouse lung tissue contains few MCPs and MCs, and these cellular reservoirs are not affected by the lack of α chemokine receptor 2 or α4β7 integrin. Nonetheless, robust recruitment of MCPs to the lung occurs during experimentally induced allergic pulmonary inflammation and requires α4β7 and α4β1 integrins interacting with vascular cell adhesion molecule 1 but not with mucosal addressin cell adhesion molecule 1. Thus although MCs are present in all organs, the pathways responsible for the trafficking of MCPs from the circulation are organ specific and include both constitutive and inducible systems, ensuring both resident MCs and the potential for incremental recruitment in accord with the requirements of the immune response. These findings in mice await confirmation in human subjects.

Key words: Mast cells, basophils, progenitors, homing, recruitment

Abbreviations used: BaP, Basophil progenitor, BMCP, Basophil–mast cell progenitor, CCR, β Chemokine receptor, CMP, Common myeloid progenitor, CTMC, Connective tissue mast cell, CXCR, α Chemokine receptor, GMP, Granulocyte-macrophage progenitor, MAdCAM-1, Mucosal addressin cell adhesion molecule 1, MC, Mast cell, MCP, Mast cell progenitor, MMC, Mucosal mast cell, PI-3K, Phosphoinostinol-3 kinase, SCF, Stem cell factor, VCAM-1, Vascular cell adhesion molecule 1