Basophils, histamine synthesis

Although mast cells and basophils probably account for >90% of stored histamine in the body, histamine is also present in platelets, enterochromaffin-like cells, endothelial cells, and neurons. Histamine can act as a neurotransmitter in the brain. Histaminergic nerves have their cell bodies within a very small area of the brain (the magnocellular nuclei of the posterior hypothalamus) but have axons in most areas of the forebrain. There is also evidence for axons projecting into the spinal (Fig. 1) cord. Finally, there is evidence that histamine synthesis can be induced in tissues undergoing rapid tissue growth and repair. In certain neonatal tissues (e.g. liver), the rate of synthesis of this unstored diffusable histamine (termed nascent histamine) is profound and may point to a role for histamine is cell proliferation. 

H3 receptor activation in the airway system of the guinea pig caused a decrease in histamine release from mast cell and/or basophils and the H3 antagonist had the opposite effect. As far as histamine synthesis is concerned, the allergen-exposure induced histamine forming capacity could be increased by thioperamide, even though (R)a-methylhistamine was completely inactive. The explanation given for this peculiar phenomenon was that the histamine... 

Synthesis. Histamine [51-45-6] 2-(4-imidazolyl)ethylarnine (1) is formed by decarboxylation of histidine by the enzyme L-histidine decarboxylase (Fig. 1). Most histamine is stored preformed in cytoplasmic granules of mast cells and basophils. In humans mast cells are found in the loose connective tissue of all organs, especially around blood and lymphatic vessels and nerves. These cells are most abundant in the organs expressing allergic diseases the skin, respiratory tract, and gastrointestinal tract. 

Type I allergic reactions are inappropriate immune responses to an allergen with preferential synthesis of immunoglobulin E (IgE), a special antibody class, which binds to mast cells and basophilic granulocytes via Fee receptors. Binding of the allergen to the cell-bound IgE initiates the rapid release of allergic mediators, most prominently histamine, and the de novo synthesis of arachidonic acid metabolites and cytokines, which are responsible for the clinical symptoms. 

The classical cellular sources of histamine are mast cells and basophils, gastric enterochromaffin-like cells, platelets and histaminergic neurons. Interestingly the cells in the immune system, which do not store histamine, show high HDC activity and are capable of production of high amounts of histamine, which is secreted immediately after synthesis [20]. These cells include platelets, monocytes/macrophages, DCs, neutrophils, and T and B lymphocytes. 

Glucocorticosteroids are the most potent antiinflammatory agents available. They stabilize lysosomal membranes and reduce the concentration of proteolytic enzymes at the site of inflammation. They promote the synthesis of proteins called lipocortins which inhibit phospholipase-A2 and thus inhibit production of arachidonic acid, leukotrienes and prostaglandins. Furthermore, the expression of COX-II and through that the inflammatory effects of the licosanoids is inhibited. Glucocorticosteroids reduce the release of histamine from basophils, decrease capillary permeability and cause vasoconstriction. Glucocorticosteroids stimulate the loss of calcium with the urine and inhibit the resorption of calcium from the gut. 

Histamine is synthesized from the amino acid histidine by an action of the enzyme histidine decarboxylase (Fig. 38.1). Following synthesis, histamine is either rapidly inactivated or stored in the secretory granules of mast cells and basophils as an inactive complex with proteases and heparin sulfate or chondroitin sulfate. 

Synthesis. Histamine, 2-(4-imidazolyl)ethylamine, is formed by decarboxylation of histidine by the enzyme l.-histidinc decarhoxylase. Most histamine is stored preformed in cytoplasmic granules of mast cells and basophils. 

Synthesis Histamine is an amine formed by the decarboxylation of the amino acid histidine (Figure 40.3). This process occurs primarily in the mast cells, basophils, and in the lungs, skin, and gastrointestinal mucosa—the same tissues in which histamine is stored. In mast cells, histamine is stored in granules as an inactive complex composed of histamine and the polysulfated anion, heparin, along with an anionic protein. If histamine is not stored, it is rapidly inactivated by amine oxidase enzymes. 

Glucocorticoids also have antiallergic properties, as a result of and by an inhibition of the synthesis of histamine by mast cells and basophils. Of the naturally occurring corticosteroids, only cortisol and corticosterone possess glucocorticoid activity, with cortisol the most effective. Cortisone and 11-dehydrocorticosterone lack direct glucocorticoid activity, but have potential glucocorticoid activity because they can be metabolixed to cortisol and corticosterone, respectively. 

Epinephrine and isoproterenol (via cAMP mechanisms) and theophylline (via cAMP or block of adenosine receptors) inhibit the release of mediators from mast cells and basophils and cause bronchodilation. Diphenhydramine competitively blocks histamine actions at H, receptors, actions that would otherwise cause bronchoconstriction and increased capillary permeability. Dexamethasone has multiple cellular effects, including inhibition of IgE-producing clone proliferation, block of T helper cell function, and anti-inflammatory actions. Most of the actions of glucocorticoids result from decreases in the synthesis of cytokines (eg, interleukins, platelet activating factor) or eicosanoids (leukotrienes, prostaglandins). 

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