Flavonoids and other polyphenols are ubiquitous in plants including edible fruits, vegetables and tobacco. Free polyphenols have been known to affect a number of biochemical processes. Our recent studies of the effects of a rutin (R) containing glycoprotein, which is purified from cured tobacco leaves (TGP), suggest that polyphenol containing compounds might be important environmental substances which can affect many biological systems in addition to their role as antigens, TGP, which can be regarded as a prototype for flavonoid containing compounds, is pharmacologically and immunologically unusual in that it: activates factor XII (Hageman factor); inhibits C2; elicits primarily or exclusively a specific IgE response in mice, guinea pigs and neonatal rabbits; elicits immediate cutaneous hypersensitivity reactions in one-third of normal human volunteers; is a T-cell independent B-cell mitogen for mice; is mitogenic for human peripheral blood lymphocytes; and binds specifically to the murine dendritic-like cell line DEN-1. The rutin moiety is important in some of these effects. We propose to determine if the selective expression of IgE in response to rutin containing compounds is due to preferential activation of T helper cells specific for IgE or to preferential activation of T suppressor cells for isotypes other than IgE. In addition, the role of dendritic cells in the IgE response to TGP in vivo and in the mitogenic effects of TGP in vitro will be determined. We will produce monoclonal antibodies to dendritic cells to assist in characterizing their function. The specific binding of TGP and R- BAS to DEN-1 suggest the presence of a receptor on the plasma membrane. This might be of great significance in the function of dendritic cells as accessory cells. We, therefore, propose to identify and characterize the putative receptor. We will determine: affinity of binding, the density of receptors, the specificity of the binding and the nature of the receptor (e.g. is it a protein). We propose to isolate the rutin binding component on the dendritic cell membrane, to characterize it and to prepare antibodies specific for it. The proposed research will study the interaction between a class of ubiquitous, and important environmental stimuli, dendritic cells, regulation of isotype expression and induction of lymphocyte proliferation.
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