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 fuctuations, which tend to occur due to variation in the histamine content of the food, histamine production by microfora, 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, H1R and H2R. In contrast, the nonprofessionally-produced, low nascent histamine levels are only able to activate two novel high-affinity histamine receptors, H3R and H4R. 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/H1R/H2R amplifies expulsion of irritants (e.g. pollen, helminths) by adding to a direct irritant-induced reaction an amplifying IgE-dependent immunological component. Nanomolar histamine/H3R/H4R seems to participate in dendritic cell-mediated antigen (Ag) presentation to T-cells in induction of self-tolerance, sensitization phase in allergy and delayed lymphocyte-mediated immune reactions. From this point of view, it is interesting that H4R is best known for being expressed by myelopoietic cells, such as dendritic cells and lymphocytes, but also polymorphonuclear neutrophils, basophils, eosinophils and mast cells (MC). The role of histamine has been mainly recognized during exacerbation of asthma, allergic rhinitis and conjunctivitis, urticaria and anaphylaxis as well as gastric acid secretion after a meal. Antihistamines are generally helpful during the acute stages of various allergic states associated with burst release of histamine. However, it seems that the basis of these conditions lies in a steadier underlying immune activity, e.g. Ag presentation by dendritic cells to T-cells and T-cell help to B-cell-dependent IgE immunoglobulin synthesis against T-celldependent Ag. Normally this system participates in the maintenance of health (immune tolerance and immune responses against pathogens), but in patients it can participate in the initiation and perpetuation of diseases and contributes to the recurrence of the symptoms and signs upon renewed exposure to the symptom triggers (allergens in allergies and auto-Ag in autoimmune diseases). Therefore, antihistamines or H1R-antagonists and H2R blockers provide limited therapeutic effectiveness in such conditions, but these conditions may in part be regulated by low histamine and high-affinity histamine receptors, in particular H4R. Histamine H4R modulation by small molecules administered perorally or locally might provide effective and affordable new remedies for various autoinflammatory, allergic and autoimmune diseases.

Non-professional Histamine Producing Cells, Immune Responses and Autoimmunity / Konttinen, Yrjö T.; Henrik, Husu; Xia, Han; Passani, M. Beatrice; Clara, Ballerini; Vasily, Stegaev; Tarvo, Sillat; Zygmunt, Mackiewicz. - STAMPA. - (2013), pp. 201-258. [10.2478/9788376560564.c7]

Non-professional Histamine Producing Cells, Immune Responses and Autoimmunity

PASSANI, MARIA BEATRICE;BALLERINI, CLARA;
2013

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 fuctuations, which tend to occur due to variation in the histamine content of the food, histamine production by microfora, 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, H1R and H2R. In contrast, the nonprofessionally-produced, low nascent histamine levels are only able to activate two novel high-affinity histamine receptors, H3R and H4R. 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/H1R/H2R amplifies expulsion of irritants (e.g. pollen, helminths) by adding to a direct irritant-induced reaction an amplifying IgE-dependent immunological component. Nanomolar histamine/H3R/H4R seems to participate in dendritic cell-mediated antigen (Ag) presentation to T-cells in induction of self-tolerance, sensitization phase in allergy and delayed lymphocyte-mediated immune reactions. From this point of view, it is interesting that H4R is best known for being expressed by myelopoietic cells, such as dendritic cells and lymphocytes, but also polymorphonuclear neutrophils, basophils, eosinophils and mast cells (MC). The role of histamine has been mainly recognized during exacerbation of asthma, allergic rhinitis and conjunctivitis, urticaria and anaphylaxis as well as gastric acid secretion after a meal. Antihistamines are generally helpful during the acute stages of various allergic states associated with burst release of histamine. However, it seems that the basis of these conditions lies in a steadier underlying immune activity, e.g. Ag presentation by dendritic cells to T-cells and T-cell help to B-cell-dependent IgE immunoglobulin synthesis against T-celldependent Ag. Normally this system participates in the maintenance of health (immune tolerance and immune responses against pathogens), but in patients it can participate in the initiation and perpetuation of diseases and contributes to the recurrence of the symptoms and signs upon renewed exposure to the symptom triggers (allergens in allergies and auto-Ag in autoimmune diseases). Therefore, antihistamines or H1R-antagonists and H2R blockers provide limited therapeutic effectiveness in such conditions, but these conditions may in part be regulated by low histamine and high-affinity histamine receptors, in particular H4R. Histamine H4R modulation by small molecules administered perorally or locally might provide effective and affordable new remedies for various autoinflammatory, allergic and autoimmune diseases.
2013
9788376560564
Histamine H4 Receptor: A Novel Drug Target in Immunoregulation and Inflammation
201
258
Konttinen, Yrjö T.; Henrik, Husu; Xia, Han; Passani, M. Beatrice; Clara, Ballerini; Vasily, Stegaev; Tarvo, Sillat; Zygmunt, Mackiewicz
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1058107
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