摘要：

We previously showed that cultured human umbilical vein endothelial cells (HEC) exposed to the inflammatory cytokines tumor necrosis factor-α or interleukin-1 display increased activity of β-galactoside α2,6-sialyltransferase. This is associated with enhanced expression of ligands for the B cell receptor CD22β, which recognizes α2-6-linked sialic acids (Hanasaki, K., Varki, A., Stamenkovic, I., and Bevilacqua, M. P.(1994) 269, 10637-10643). Here we report that increased expression of CD22 ligands is a feature of dermal microvascular endothelial cells as well, and is also observed in response to the cytokine interleukin-4. Tumor necrosis factor-α stimulation of HEC causes no change in the profile of endothelial glycoproteins recognized by CD22, but doubles the proportion of total cellular -linked oligosaccharides capable of binding tightly to CD22. This modest change is sufficient to cause a marked increase in α2-6-linked sialic acid-dependent binding of Chinese hamster ovary (CHO) cells expressing recombinant human CD22. In contrast, B lymphoma cell lines expressing higher levels of cell surface CD22 do not show such sialic acid-dependent binding to activated HEC. Since B lymphoma cells themselves also express high levels of α2-6-linked sialic acids, their CD22 molecules might be rendered nonfunctional by endogenous ligands. In support of this, the lectin function of CD22 can be directly detected on transfected CHO cells, but not on B lymphoma cells. Furthermore, coexpression of β-galactoside α2,6-sialyltransferase with CD22 in the CHO cells abrogates sialic acid-dependent binding to cytokine-activated HEC. However, such co-transfected cells can bind to B lymphoma cells in a manner apparently less dependent upon α2-6-linked sialic acid, suggesting CD22-mediated interactions that may not be directly dependent on its lectin function. Thus, CD22-mediated interactions between B cells and activated vascular endothelium may be positively regulated by induction of α2-6-linked sialic acid-bearing endothelial cell ligands, but negatively regulated by such ligands on the B cells expressing CD22. Since expression of both CD22 and β-galactoside α2,6-sialyltransferase are regulated during B cell ontogeny, these findings could be of importance in B cell function and/or trafficking.

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