Histamine, histamine receptors and their role in immune pathology

Abstract

The important roles of histamine in body physiology and various pathologic events have been well established, whereas new and exciting findings are still being uncovered. Histamine is not only the major mediator of the acute inflammatory and immediate hypersensitivity responses, but has also been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. The diverse effects of histamine on immune regulation are due to the differential expression and regulation of four histamine receptors (HR) and their distinct intracellular signals. Differences in the affinities of these receptors are highly decisive on the biological effects of histamine and agents that target HRs. In particular, the discovery of reciprocal regulation of T cell activity by H1 and H2 receptor activation indicating histamine-cytokine cross-talk, as well as the characterization of the fourth histamine receptor (HR4) and its expression on numerous immune and inflammatory cells have prompted a re-evaluation of the actions of histamine. This accounts for a new potential for HR antagonists and agonists in targeting various immunopathologic conditions.

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

“…There were also some modulated genes with important anti-inflammatory properties in 6-dpf fish: the histamine receptor H2 (HRH2), that acts as a suppressor of antigen presentation capacity and enhances IL10 production [58][59][60][61][62][63] and the toll IL1 receptor domain-containing adaptor (SARM1) that down-modulates NFKB and IRF3-mediated TLR3 and TLR4 signaling. 64 Similar to the LD treatment, some proteins related to tissue damage and apoptosis were also modulated in zebrafish in response to the SLD treatment, but the inflammatory effects did not seem to be as apparent as for the lethal treatment.…”

Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal

“…15,16 However, platelets, dendritic cells (DCs), T cells, and even microbes can also express histidine decarboxylase following a stimulation by cytokines, including IL-1, IL-3, IL-12, IL-18, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and TNF-α. 13,17,18 Only MCs and basophils are capable of storing large quantities of histamine. Other cell types such as DCs and lymphocytes do not store histamine intracellularly but the synthesis is followed by an immediate secretion.…”

“…13 Histamine is synthesized by the enzyme histidine decarboxylase in all human tissues, but is particularly abundant in the skin, lungs, and GI tract. 14 Histamine is produced mainly by MCs and, to a lesser extent, by basophils, gastric enterochromaffin-like cells, and histaminergic neurons.…”

Practical Use of Acoustic Rhinometry for Quantitative Assessment of Nasal Obstruction in an Allergic Model Using Macaque Monkeys

“…Thus, fexofenadine significantly ameliorated post-challenge nasal congestion, although the recovery was not complete. Fexofenadine is an inverse agonist of the histamine H1 receptor, and it functions by blocking constitutive activation of receptors stimulated by histamine [11]. The H1 receptor consists of an active and inactive conformation coexisting in equilibrium.…”