Publications

The manifestations of allergic disorders are closely tied to the biologic effects of IgE activation with Ag. In immediate hypersensitivity reactions, IgE effector function requires prior binding to innate immune cells, primarily mast cells and basophils, with the blood acting as a reservoir for unbound IgE. As the severity of allergic disease is proportional to the size of this unbound IgE pool, we hypothesized that cellular mechanisms exist to limit the size and/or enhance the clearance of free IgE molecules. We examined this in mice by engineering a reporter IgE molecule that allowed us to track the fate of IgE molecules in vivo. The absence of FcεRI-expressing cells did not affect serum IgE levels, but B cells regulated serum IgE by controlling the size of the free IgE pool. B cells captured IgE by direct binding to the low-affinity IgE receptor, CD23. These data indicate a mechanism regulating serum IgE and additionally clarify the role of CD23 in this process.

Heme is vital to our aerobic universe. Heme cellular content is finely tuned through an exquisite control of synthesis and degradation. Heme deficiency is deleterious to cells, whereas excess heme is toxic. Most of the cellular heme serves as the prosthetic moiety of functionally diverse hemoproteins, including cytochromes P450 (P450s). In the liver, P450s are its major consumers, with >50% of hepatic heme committed to their synthesis. Prosthetic heme is the sine qua non of P450 catalytic biotransformation of both endo- and xenobiotics. This well-recognized functional role notwithstanding, heme also regulates P450 protein synthesis, assembly, repair, and disposal. These less well-appreciated aspects are reviewed herein.