Blood borne mast cell progenitors (MCp) arise from the granulocyte-monocyte lineage in bone marrow (BM) and enter peripheral tissues by transendothelial migration in response to specific chemoattractants and adhesion molecules. We have previously demonstrated that under basal conditions there is a requirement for the beta7 integrin for MCp homing to the intestine, and have recently observed that the CXCR2 chemokine receptor is also necessary for constitutive MCp homing to the intestine. Additionally we determined that a deficit in the alphaM integrin results in a reduction in mature peritoneal and dorsal skin MCs under basal conditions without affecting the intestinal MCs. These results imply that under basal conditions tissue-specific adhesion molecules and chemoattractants differentially regulate MCp homing. However, little is currently known regarding the specific requirements for the trafficking of MCp to peripheral tissues such as the intestine and lung during inflammation. It is likely that pathways distinct from those required for constitutive homing, are required to recruit MCp to these tissues under inflammatory conditions. For example in spite of an absolute deficit in MCp and mature MCs in the intestine of beta7-deficient mice, MCs can still be recruited to the intestine following infection with Trichinella spiralis. We have induced allergic inflammation in mice using ovalbumin/alum sensitization followed by challenge with aerosolized ovalbumin. This challenge results in a simultaneous 28-fold increase in pulmonary MCp and a 4-fold increase in intestinal MCp. Additionally a significant intestinal mastocytosis is also noted in the challenged animals. We suggest that local inflammation can expand the resident MCp population while recruiting additional MCp using distinctly elicited pathways for adhesion and directed migration. Accordingly we hypothesize that the selectin, integrin, and chemokine pathway requirements for inflammatory recruitment of MCp to a peripheral tissue will introduce additional migratory pathways beyond those required for basal migration of MCp.
The aim of this proposal is to identify those pathways which are responsible for inflammatory recruitment of MCp to the lung and intestine.
| Abonia, J Pablo; Blanchard, Carine; Butz, Bridget Buckmeier et al. (2010) Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol 126:140-9 |
| DeBrosse, Charles W; Collins, Margaret H; Buckmeier Butz, Bridget K et al. (2010) Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982-1999. J Allergy Clin Immunol 126:112-9 |
| Hallgren, Jenny; Jones, Tatiana G; Abonia, J Pablo et al. (2007) Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell progenitors. Proc Natl Acad Sci U S A 104:20478-83 |
| Abonia, J Pablo; Hallgren, Jenny; Jones, Tatiana et al. (2006) Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung. Blood 108:1588-94 |
| Abonia, J Pablo; Austen, K Frank; Rollins, Barrett J et al. (2005) Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2. Blood 105:4308-13 |
