CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein

Abstract

CD34 is expressed on the surface of hematopoietic stem/progenitor cells, stromal cells, and on the surface of high-endothelial venules (HEV). CD34 binds L-selectin, an adhesion molecule important for leukocyte rolling on venules and lymphocyte homing to peripheral lymph nodes (PLN). We generated CD34-deficient mutant animals through the use of homologous recombination. Wild-type and mutant animals showed no differences in lymphocyte binding to PLN HEV, in leukocyte rolling on venules or homing to PLN, in neutrophil extravasation into peritoneum in response to inflammatory stimulus, nor in delayed type hypersensitivity. Anti-L-selectin monoclonal antibody (MEL-14) also inhibited these immune responses similarly in both CD34-deficient and wild-type mice. However, eosinophil accumulation in the lung after inhalation of a model allergen, ovalbumin, is several-fold lower in mutant mice. We found no abnormalities in hematopoiesis in adult mice and interactions between mutant progenitor cells and a stromal cell line in vitro were normal. No differences existed in the recovery of progenitor cells after 5-fluorouracil treatment, nor in the mobilization of progenitor cells after granulocyte colony-stimulating factor treatment compared with wild-type animals. Surprisingly, although CD34 was not expressed in these mice, a portion of its 90-kD band crossreactive with MECA79 remained after Western blot. Thus, we have identified an additional molecule(s) that might be involved in leukocyte trafficking. These results indicate that CD34 plays an important role in eosinophil trafficking into the lung.

The Sialomucin CD34 Is a Marker of Lymphatic Endothelial Cells in Human Tumors

“…22 CD34-deficient mice have no overt developmental phenotype but have been shown to display distinct hematopoietic defects that are compatible with the expression of CD34 by hemangioblastic stem cells. 23,24 CD34 is expressed in the adult with some heterogeneity by blood endothelial cells in most vascular beds. It is a pan-endothelial marker of microvascular endothelial cells that is not expressed by most large vessel endothelial cells.…”

“…Lack of CD34 expression in mouse tumor-associated LECs may limit the use of CD34-deficient viable mice that have no overt vascular or lymphatic phenotype. 23,24 Yet, cellular experiments in human LECs may shed light into the role of CD34 in angiogenic LEC function. Second, the exclusive expression of CD34 by tumor-associated LECs and not by normal resting organ LECs strongly suggests that CD34 is an activation antigen of human LECs.…”

CD34 is a Key Regulator of Hematopoietic Stem Cell Trafficking to Bone Marrow and Mast Cell Progenitor Trafficking in the Periphery

“…Comparison of pure bone marrowÁderived mast cells from CD34 knockout [51] and wild-type animals demonstrates that CD34 has no observable effect on proliferation, differentiation, cytokine production, or This proposed function is based on the observation that hematopoietic progenitor cells from CD34-null mice appear to proliferate less, in comparison to cells from wild-type mice [11]. (B) CD34 blocks differentiation.…”

Selectins and glycosyltransferases in leukocyte rolling in vivo

“…To further investigate the contribution of the different PNAd members for selectin ligand function in vivo , lymphocyte homing was investigated in glycosylation‐dependent cell adhesion molecule‐1 –/– mice that demonstrated normal lymphocyte trafficking [23]. Similarly, CD34 –/– mice had no defect in lymphocyte trafficking [24] suggesting that L ‐selectin ligand activity on HEV is not dependent on a single member of the PNAd family, but comprises a redundant system where the loss of one member is compensated by the presence of the others. In addition, it indicates that other regulatory mechanisms, such as post‐translational modifications, contribute to cell‐specific and activation‐specific expression of functional selectin ligands in vivo .…”