CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution.
CD34 is a cell-surface sialomucin expressed by hematopoietic stem cells (HSC), mast cells, and vascular endothelia. Despite its popularity as an HSC marker, the function of CD34 on hematopoietic cells remains enigmatic. Here, we 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, reexpression of CD34 or CD43 in these cells caused reversal of this phenotype. Furthermore, we find that loss of these sialomucins prevents mast cell repopulation and hematopoietic precursor reconstitution in vivo. Our data provide clear-cut evidence for a hematopoietic function for CD34 and suggest that it acts as a negative regulator of cell adhesion.
Drew
Erin
E
The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Merzaban
Jasmeen S
JS
Seo
Wooseok
W
Ziltener
Hermann J
HJ
McNagny
Kelly M
KM
D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects*; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology; D051917:Leukosialin; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D012795:Sialoglycoproteins / Q000494:pharmacology*
D015703:Antigens, CD; D018952:Antigens, CD34; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse