Progenitor egress from the bone marrow after allergen challenge:: Role of stromal cell-derived factor 1α and eotaxin

Background: CCR3 expression on CD34(+) cells mediates migration to cotaxin in vitro. CXCR4 and stromal cell-derived factor (SDF)-1 alpha are important for stem cell homing to hemopoietic compartments. Objective: To study chemokine-mediated progenitor cell traffic in allergic inflammation. Methods: Bone marrow (BM) aspirates were obtained at baseline from normal subjects; atopic subjects without asthma; and subjects with asthma before, 5 hours after, and 24 hours after allergen inhalation (dual and early responders). Changes in chemokine receptor expression and migration were assessed. Results: Expression of CXCR4, but not CCR3, on BM CD34(+) cells was greater in normal subjects compared with atopic subjects with asthma. Likewise, SDF-1 alpha, but not eotaxin, stimulated a greater migrational response by BM CD34(+) cells from normal subjects compared with subjects with asthma. For all subjects, a positive correlation was found between intensity of CXCR4 expression and magnitude of CD34+ cell response to SDF-1 alpha. Allergen inhalation attenuated both intensity of CXCR4 expression and SDF-1 alpha levels in marrow from dual compared with early responders 24 hours postallergen. In contrast, the intensity of CCR3 expression on BM CD34(+) cells increased in dual compared with early responders at 24 hours postallergen. In addition, an increase in migrational responsiveness of BM CD34(+) cells to eotaxin and a decrease to SDF-1 alpha 24 hours postallergen was found in dual responder subjects with asthma. Conclusion: After allergen inhalation in subjects with asthma, a downregulation in CXCR4 intensity on BM CD34(+) cells and a reduction in BM SDF-1 alpha levels may reduce progenitor retention to marrow stroma promoting peripheral egress, possibly mediated by the CCR3/eotaxin axis.