Trends in Immunology
ReviewTrends in histamine research: new functions during immune responses and hematopoiesis
Section snippets
Cellular sources of histamine
The role of mast cells and basophils as a major source of histamine in normal tissues has been reviewed extensively 1., 2. and will not be discussed here. Instead, this article will focus on other cellular sources of histamine synthesis by HDC. Several hematopoietic populations that contain neither mast cells nor basophils share this enzymatic activity 3., 4.. These cells lack specific granules for storage and the mediator is therefore secreted as soon as it has been synthesized. For this
Regulation of histamine synthesis
HDC (EC 4.1.1.22) catalyzes the formation of histamine from l-histidine. The cDNAs encoding this protein have been isolated from fetal rat liver, human basophil leukemia cells, mouse mastocytoma cells and human erythroleukemia cells. Structural studies have revealed that both mouse and human genes are composed of 12 exons, which span approximately 24 kb. The mouse gene gives rise to a single transcript of 2.4 kb, whereas two splice variants of 3.4 kb and 2.4 kb exist in humans, the latter
Histamine receptors
Until recently, the multiple biological activities of histamine were attributed to three histamine receptors (H1, H2 and H3). These receptors are heptahelical G-protein-coupled receptors (Fig. 2Table 1) that transduce extracellular signals through Gq, Gs and Gi/o, respectively. Now, not only have various forms of the H3 receptor been described 42., 43., but also a new H4 receptor, expressed mainly in hematopoietic and immunocompetent cells, has been identified [44]. This review will focus on
Biological activities of histamine
Since its discovery at the beginning of the 20th century, the array of biological activities attributed to histamine has constantly expanded. In the field of immunology, the mediator is associated mainly with its deleterious effects during allergic responses. However, more recently, the discovery of the cytokine network has led to the demonstration of more-beneficial properties of histamine, as a modulator of the cytokine profile and a mediator of certain biological effects induced by
Conclusions and future directions
In the past few years, histamine research has received a new impetus from increasing evidence for the capacity of this small molecule to exert various regulatory functions affecting the immune response and certain aspects of hematopoiesis. By now, its participation in the intricate cross-talk between cytokines and cells involved in the differentiation of Th1 and/or Th2 cells has been underlined by many studies. However, some data remain controversial, probably because of the complexity of the
Acknowledgements
This work was supported by a grant from the Association pour la Recherche contre le Cancer (ARC no. 4422). M.R-D. received a postdoctoral fund from ARC.
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