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The role of podocalyxin and CD34 in mouse models of anemia, asthma, ulcerative colitis and tumor growth

University of British Columbia

CD34, podocalyxin and endoglycan are cell surface sialomucins, which comprise the CD34-family of proteins. While many roles have been proposed for the CD34 family of molecules, little is known about their functions in disease. In a phenylhydrazine-induced model of anemia, we demonstrated that podocalyxin is rapidly induced on early stress erythroid progenitors, from an early BFU-E stage, through to immature reticulocytes. Our data suggest that although podocalyxin is not required for recovery from anemia, it can be used as a simple marker of stress erythroid progenitors. CD34 is expressed on mature inflammatory cells including mast cells, eosinophils and dendritic cell precursors. Interestingly, in an OVA-induced asthma model, Cd34-/- mice exhibited attenuated pathology and reduced immune cell infiltration into the alveoli and lung parenchyma. CD34 expression is present on lung and BAL eosinophils, and isolated Cd34-/- eosinophils exhibit a migration defect in vitro. These findings suggest a key role for CD34 in asthma pathology. Similarly, in a dextran sulfate sodium-induced colitis model, Cd34-/- mice exhibited significantly reduced pathology, associated with loss of CD34 expression on colon-infiltrating eosinophils. Eosinophil numbers were reduced in Cd34-/- tissues and induction of hypereosinophilia in Cd34-/- mice was sufficient to overcome the protection from DSS-induced disease. Thus, we have also demonstrated a key role for CD34 and eosinophil trafficking in ulcerative colitis. Finally, in a B16 melanoma tumor model, Cd34-/- mice exhibit altered tumor growth kinetics. At early stages, Cd34-/- mice exhibited reduced tumor size, due to loss of CD34 expression on non-hematopoietic cells (likely vascular endothelial cells). Conversely, at later timepoints, Cd34-/- mice exhibited increased tumor growth, due to loss of CD34 expression on hematopoietic cells. These findings suggest complex, opposing roles for CD34 in tumor growth due to effects on vascular integrity in early disease and immune cell-mediated tumor rejection later in the disease. These findings suggest key roles for CD34-family proteins in a range of disease states. Podocalyxin expression is induced during embryonic and stress erythropoiesis and is an indicator of anemia. CD34 plays a key role in optimal immune cell migration during asthma, colitis and tumor growth.

Text

2010-12-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/25969

Genetics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/