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 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.
Blanchet
Marie-Renée
MR
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Maltby
Steven
S
Haddon
D James
DJ
Merkens
Helen
H
Zbytnuik
Lori
L
McNagny
Kelly M
KM
D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000502:physiology*; D001249:Asthma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow; D002448:Cell Adhesion; D002465:Cell Movement; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000209:etiology
D018952:Antigens, CD34; D010047:Ovalbumin