Date of Award

Fall 2011

Degree Type


Degree Name

Master of Science in Medical Sciences (MSMS)


Medical Sciences


Roma Sehmi


Parameswaran Nair, Mark Inman



Committee Member

Parameswaran Nair, Mark Inman


Rationale: Lung-homing of bone marrow (BM)-derived progenitor cells is associated with inflammatory and remodeling changes in asthma. Stromal cell derived factor-1α (SDF-1α) is a potent progenitor cell chemoattractant and its local production in the lung promotes lung homing of progenitor cells. The role of pro-inflammatory cytokines in promoting traffic of progenitor cells to the site of inflammation in asthma has not been investigated. The TH2 cytokines, interleukin (IL)-4 and IL-13, are key regulators of asthma pathology.

Objective: To investigate the role of IL-4 and IL-13 in modulating the trans-migrational responses of hemopoietic progenitor cells (HPC).

Methods: HPC were isolated from cord blood (CB) and peripheral blood (PB) and migrational and adhesive responses were assessed using transwell migration assays and adhesion to fibronectin-coated wells, respectively. Responding cells were enumerated by flow cytometry.

Results: IL-4 and IL-13 had no direct effect on progenitor cell migration. Pre-incubation with each of these cytokines primed SDF-1α stimulated migration of CB and PB-derived HPC (CD34+45+ cells) but not eosinophil-lineage committed progenitors (CD34+45+IL- 5Rα+ cells) or mature eosinophils to SDF-1α. For HPC, priming effects of IL-4 (0.1ng/ml) and IL-13 (0.1ng/ml) were detectable within 1hr and optimal at 18hr post- incubation and IL-4 was the more effective priming agent. Disruption of lipid rafts inhibited IL-4 priming of SDF-1α stimulated migration of HPC indicating that increased incorporation of CXCR4 into membrane lipid rafts mediates the cytokine primed migrational response of HPC. This was confirmed by confocal fluorescent microscopy.

Conclusions: IL-4 and IL-13 prime the migrational response of HPC to SDF-1α by enhancing the incorporation of CXCR4 into lipid rafts. The priming effect of these cytokines is specific to primitive HPC. These data suggest that increased local production of IL-4 and IL-13 within the lungs may promote increased SDF-1α mediated homing of BM-derived HPC to the airways in asthma.

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