Chapter 7 Non-professional Histamine Producing Cells, Immune Responses and Autoimmunity

Abstract

Histamine is a monovalent cationic biological amine synthesized by professional and non-professional histamine producing cells, which form two distinct cell categories. Professional cells produce, store and burst release their histamine from storage granules so that locally and temporarily for short periods high micromolar histamine concentrations are achieved. Non-professional cells generally produce and release histamine into the cytoplasm continuously without intermediated storage, to release it along its concentration gradient via histamine channels. These channels might play an important role in balancing, maintaining and regulating low-level histamine fluctuations, which tend to occur due to variation in the histamine content of the food, histamine production by microflora, histamine release from professional cells and enzymatic degradation and reuptake of histamine. Effects of the professionally-produced high histamine levels are mediated via two low-affinity histamine receptors, H 1 R and H 2 R. In contrast, the nonprofessionally-produced, low nascent histamine levels are only able to activate two novel high-affinity histamine receptors, H 3 R and H 4 R. The former are active during short-term emergency "on-state" whereas the latter are active during a basic or long term homeostatic "off-state". Micromolar histamine/H 1 R/H 2 R amplifies expulsion of irritants (e.g. pollen, helminths) by adding to a direct irritant-induced