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UBC Theses and Dissertations

CD34 and CD43 block mast cell adhesion and are required for optimal mast cell reconstitution Drew, Erin Christina

Abstract

CD34 is a cell surface sialomucin expressed by hematopoietic stem cells (HSC) and vascular endothelia and is widely used for the enrichment of human hematopoietic stem cells because of its selective expression on progenitor cells and absence on mature hematopoietic cells. Although CD34 was undetectable in all murine progenitor cell lines tested, high expression was detected in bone marrow-derived mast cells (BMMC) and in peritoneal mast cells analyzed in vivo. Our results demonstrate that, contrary to current dogma, CD34 is expressed by one mature hematopoietic lineage: mast cells. Our data also demonstrate that antigenically, murine mast cells, and their precursors, closely resemble HSC. However, in contrast, human CD34 is not expressed by human mast cells, and this dichotomy represents a regulatory difference for this protein between these two species. Despite its popularity as an HSC marker, the function of CD34 on hematopoietic cells remains enigmatic. Here I have addressed this issue by examining the behavior of mutant mast cells lacking CD34, the related sialomucin, CD43, or both molecules. Loss of these molecules leads to a gene-dose-dependent increase in mast cell homotypic aggregation with CD34/CD43KOs > CD43KO > CD34KO > wild type. Importantly, re-expression of CD34 or CD43 in these cells caused reversal of this phenotype. Furthermore, I found that loss of these sialomucins prevented mast cell repopulation and hematopoietic precursor reconstitution in W/W[sup v] recipients. However, the ability of these cells to reconstitute lethally irradiated wild type mice is not impaired, presumably due to irradiation induced differences within the host. Our data provide the first clear-cut evidence for a hematopoietic function for CD34 and suggest that it acts as a negative regulator of cell adhesion.

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