Allergen-induced, eotaxin-rich, proangiogenic bone marrow progenitors: A blood-borne cellular envoy for lung eosinophilia

Background: Eosinophilic inflammation is closely related to angiogenesis in asthmatic airway remodeling. In ovalbumin (OVA) sensitized mice bone marrow derived, proangiogenic endothelial progenitor cells (EPCs) are rapidly recruited into the lungs after OVA aerosol challenge and promptly followed by mobilization and recruitment of eosinophils. Objective: We hypothesized that bone marrow derived EPCs initiate the recruitment of eosinophils through expression of the eosinophil chemoattractant eotaxin-1. Methods: EPCs were isolated from an OVA murine model of allergic airway inflammation and from asthmatic patients. Endothelial and smooth muscle cells were isolated from mice. Eotaxin-1 expression was analyzed by means of immunofluorescence, real-time PCR, or ELISA. In vivo recruitment of eosinophils by EPCs was analyzed in mice. Results: Circulating EPCs of asthmatic patients had higher levels of eotaxin-1 compared with those seen in control subjects. In the murine model OVA allergen exposure augmented eotaxin-1 mRNA and protein levels in EPCs. The EPCs from OVA-sensitized and OVA-challenged mice released high levels of eotaxin-1 on contact with lung endothelial cells from sensitized and challenged mice but not from control animals and not on contact with cardiac or hepatic endothelial cells from sensitized and challenged mice. Intranasal administration of the eotaxin-rich media overlying cultures of EPCs caused recruitment into the lungs, confirming functional chemoattractant activity. Conclusions: Bone marrow derived EPCs are early responders to environmental allergen exposures and initiate a parallel switch to a proangiogenic and proeosinophilic environment in the lungs of asthmatic patients. (J Allergy Clin Immunol 2010;125:918-25.)