RT Journal Article
SR Electronic
T1 Modulating progenitor accumulation attenuates lung angiogenesis in a mouse model of asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj01332-2010
DO 10.1183/09031936.00133210
A1 T.M. Doyle
A1 R. Ellis
A1 H.J. Park
A1 M.D. Inman
A1 R. Sehmi
YR 2010
UL http://erj.ersjournals.com/content/early/2010/11/11/09031936.00133210.abstract
AB Asthmatic responses are associated with the lung-homing of bone marrow (BM)-derived progenitors implicated as effectors of disease pathology. Increases in lung-extracted vascular endothelial progenitors (VEPC) correlate with airway angiogenesis and declining lung function. We investigated the effect of modulating lung-homing of VEPC on tissue remodeling and airway hyperesponsiveness (AHR).Balb/C mice were sensitized to ovalbumin (OVA), subjected to a chronic exposure protocol and given early concurrent or delayed treatment with a modulator of progenitor traffic AMD3100, (CXCR4 antagonist; inhibits chemotactic activity of SDF-1alpha on VEPC). Post-OVA challenge, early hemopoietic stem cells (HSC) and VEPC were enumerated as well as indices of airway inflammation, lung morphometry and AHR.Following OVA challenge, there was decrease in BM and an associated increase in the lung tissue-extracted HSC and VEPC cells together with increases in airway eosinophilia, microvessel density and AHR. These outcomes were significantly inhibited by early concurrent treatment with AMD3100. Where lung disease was established, delayed treatment with AMD3100 significantly attenuated HSC numbers and lung angiogenesis but only partially reversed sustained AHR compared to untreated OVA exposed mice.Progenitor lung-homing is associated with the development of asthma pathology and early modulation of this accumulation can prevent airway remodeling and lung dysfunction.