Sialomucins in Inflammation and Hematopoiesis
Mucin-like glycoproteins are expressed in a diverse set of tissues. However, the functions of most of these mucins are currently unknown. One of the most interesting possibilities is that these highly glycosylated molecules perform functions that go beyond the currently accepted roles as lubricants and anti-pathogens. We have investigated the functions of two sialomucins, GlyCAM 1 and CD34, in inflammation and hematopoiesis. Both of these mucins can function as ligands for L selectin by presenting unique carbohydrates to the lectin domain of this leukocyte adhesion molecule. GlyCAM 1 is a soluble ligand for L selectin, and the production in knockout mice has revealed that this mucin appears to function as a regulator of lymphocyte trafficking during inflammation. The expression of this mucin appears to be upregulated on the endothelium during inflammation, suggesting that it might function to dampen the influx of leukocytes. Like GlyCAM 1, CD34 can also function as a ligand for L selectin-mediated adhesion. This mucin is expressed on a diversity of endothelial sites in the adult and in the embryo. In addition, it is also expressed on hematopoietic progenitors in both the adult and in the embryo. The expression of CD34 on hematopoietic cells of the yolk sac has lead to the finding that this fraction of cells contains the hematopoietic progenitors, a result that is similar to what has been found in later stages of hematopoiesis. This suggests that CD34 may play a critical role in hematopoiesis, and knockout studies in cell culture support this hypothesis. Thus, embryonic stem cells that have had both alleles of CD34 knocked out have defects in the production of hematopoietic cells when they are allowed to develop into embryoid bodies in culture. We are also currently assessing the role of CD34 in vivo in knockout mice. In summary, it appears that both GlyCAM 1 and CD34 play important roles in inflammation and hematopoiesis, consistent with the possibility that sialomucins perform a complex variety of functions.