Histamine pumped back into basophil precursor cells inhibits further synthesis of histamine.

Allergy-provoking histamine keeps itself under control, according to a study on page 387. Schneider and colleagues show that basophil precursor cells pump released histamine back into themselves. Once inside, the histamine shuts off its own production and that of allergy-promoting T helper (Th) 2 cytokines.

Basophils and mast cells are the primary histamine producers of the immune system. In mature cells, histamine is stored in intracellular granules and is rapidly released when the cells are stimulated. Once released, histamine triggers acute allergy symptoms by binding to its receptors on vascular endothelial cells and bronchial smooth muscle cells. Histamine can also be produced by nongranular cells, including macrophages and dendritic cells, which secrete the molecule immediately after synthesis.

This group previously described a population of low-granule basophil precursor cells in the bone marrow that produce histamine and Th2 cytokines. This cell population increases in size during worm infections and may help resolve infection by promoting a protective Th2 response. The authors had noted that these cells could take up histamine from the external environment, but neither the mechanism nor the consequences of this uptake were understood. Schneider et al. now show that the uptake of histamine by these cells triggers a negative feedback loop that inhibits additional histamine synthesis and the production of allergy-promoting cytokines.

Histamine transport was dependent on a cation transporter protein (organic cation transporter 3, or OCT3), which was known to transport histamine in brain cells but had never been identified on basophils. The authors speculate the reverse histamine transport may help limit the severity of allergic responses. They are now testing this idea by assessing allergic responses in OCT3-deficient mice.