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

• Published in: Journal of allergy and clinical immunology Vol. 115; no. 3; pp. 501 - 507
• Main Authors: Dorman, Sandra C., Babirad, Irene, Post, Julia, Watson, Rick M., Foley, Ronan, Jones, Graham L., O'Byrne, Paul M., Sehmi, Roma
• Format: Journal Article
• Language: English
• Published: Mosby, Inc 2005
• Subjects: asthma; CD34; eotaxin-CCR3; progenitor cell mobilization; SDF-1α–CXCR4; progenitor cell mobilization; asthma; BM; FACS; rmANOVA; SDF-1α–CXCR4; FITC; SDF; eotaxin-CCR3; HPSC; WBC; SMFI; CD34
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2004.11.017

CCR3 expression on CD34 + cells mediates migration to eotaxin in vitro. CXCR4 and stromal cell–derived factor (SDF)–1α are important for stem cell homing to hemopoietic compartments. To study chemokine-mediated progenitor cell traffic in allergic inflammation. 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. Expression of CXCR4, but not CCR3, on BM CD34 + cells was greater in normal subjects compared with atopic subjects with asthma. Likewise, SDF-1α, 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-1α. Allergen inhalation attenuated both intensity of CXCR4 expression and SDF-1α 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-1α 24 hours postallergen was found in dual responder subjects with asthma. After allergen inhalation in subjects with asthma, a downregulation in CXCR4 intensity on BM CD34 + cells and a reduction in BM SDF-1α levels may reduce progenitor retention to marrow stroma promoting peripheral egress, possibly mediated by the CCR3/eotaxin axis.