CD34 facilitates the development of allergic asthma

Asthma is a pulmonary inflammatory disease dependent on eosinophil and mast cell infiltration into the lung. CD34 is a sialomucin expressed by both of these cell types, and we have used CD34−/− mice and a standard mouse model of asthma to evaluate the importance of CD34 expression on disease develop...

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Veröffentlicht in:Blood 2007-09, Vol.110 (6), p.2005-2012
Hauptverfasser: Blanchet, Marie-Renée, Maltby, Steven, Haddon, D. James, Merkens, Helen, Zbytnuik, Lori, McNagny, Kelly M.
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Sprache:eng
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Zusammenfassung:Asthma is a pulmonary inflammatory disease dependent on eosinophil and mast cell infiltration into the lung. CD34 is a sialomucin expressed by both of these cell types, and we have used CD34−/− mice and a standard mouse model of asthma to evaluate the importance of CD34 expression on disease development. In comparison with wild-type (wt) mice, CD34−/− mice exhibited a dramatic reduction in all hallmarks of allergic asthma, including lowered airway inflammatory cell infiltration, airway hyperresponsiveness, and mast-cell recruitment. Bone marrow transplantation experiments confirmed that these defects are due to CD34 expression by bone marrow–derived cells. This was not, however, due to an inability to respond to antigen as, on a per cell basis, wt and CD34−/− inflammatory cells exhibit identical responses in cytokine production. We found a striking reduction in mobility of CD34−/− eosinophils in vitro, the major component of inflammatory infiltrates, which was consistent with proposed models for CD34 as an inhibitor of cell-cell adhesion. In summary, our data suggest that CD34 enhances mast-cell and eosinophil invasiveness and that its expression by these cells is a prerequisite for development of allergic asthma.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2006-12-062448