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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2005-2012.
Prepublished online as a Blood First Edition Paper on June 8, 2007; DOI 10.1182/blood-2006-12-062448.
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Submitted December 14, 2006
Accepted June 7, 2007
CD34 facilitates the development of allergic asthma
Marie-Renee Blanchet, Steven Maltby, D. James Haddon, Helen Merkens, Lori Zbytnuik, and Kelly M McNagny*
The Biomedical Research Center, University of British Columbia, Vancouver, BC, Canada
* Corresponding author; email: kelly{at}brc.ubc.ca.
Asthma is a pulmonary inflammatory disease dependent on eosinophil and mast cell infiltration into the lung. CD34 is a sialomucin expressed by both 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 to wild-type (wt) mice, cd34-/- mice exhibited a dramatic reduction in all hallmarks of allergic asthma, including lowered airway inflammatory cell infiltration, airway hyper-responsiveness 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.
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