Vascular permeability, histamine

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

The human histamine Hi-receptor is a 487 amino acid protein that is widely distributed within the body. Histamine potently stimulates smooth muscle contraction via Hi-receptors in blood vessels, airways and in the gastrointestinal tract. In vascular endothelial cells, Hi-receptor activation increases vascular permeability and the synthesis and release of prostacyclin, plateletactivating factor, Von Willebrand factor and nitric oxide thus causing inflammation and the characteristic wheal response observed in the skin. Circulating histamine in the bloodstream (from, e.g. exposure to antigens or allergens) can, via the Hi-receptor, release sufficient nitric oxide from endothelial cells to cause a profound vasodilatation and drop in blood pressure (septic and anaphylactic shock). Activation of... 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

This mediator, apart from aggregating platelets and stimulating many cells types, is a very potent mediator in allergic reactions causing bronchoconstriction with a 1,000 times more potency than histamine. It is able to increase vascular permeability and cause chemotaxis and degranulation of eosinophils and neutrophils [14-16]. 

Dietary copper deficiency increases the acute inflammatory response in rats and other small laboratory animals (Schuschke et al. 1994). The release of inflammatory mediators, such as histamine and serotonin, from mast cells increases the vascular permeability of postcapillary venules and results in edema. In copper-deficient rats, release of histamine from mast cells correlates positively with frequency of the acute inflammatory response. Copper-deficient rats (0.6 mg Cu/kg DW ration for 4 weeks) have more mast cells in muscle than copper-adequate controls given diets containing 6.3 mg Cu/kg DW ration however, histamine content of mast cells is not affected (Schuschke et al. 1994). An early clinical sign of copper deficiency is a reduction in the number of circulating neutrophils the mechanism for copper-deficient neutropenia (leukopenia in which... 

Vasoactive substances (histamine, kinins, prostaglandins) are released at sites of inflammation, increasing blood flow and vascular permeability. This causes edema, warmth, erythema, and pain and makes it easier for granulocytes to pass from blood vessels to sites of inflammation. 

An immediate reaction occurs within seconds to minutes, resulting in the rapid release of preformed mediators and newly generated mediators from the arachidonic acid cascade. Mediators of immediate hypersensitivity include histamine, leukotrienes, prostaglandin, tryptase, and kinins. These mediators cause vasodilation, increased vascular permeability, and production of nasal secretions. Histamine produces rhinorrhea, itching, sneezing, and nasal obstruction. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Figure 4.1. Model of neurogenic inflammation. Stimulation at the skin initiates orthodromic impulses in sensory nerve receptors which elicit antidromic impulses in branching collaterals. The release of neuropeptides such as calcitonin gene-related peptide (CGRP), substance P (SP), and somatostatin (SOM) from nerve terminals ensues and they in turn stimulate the release of histamine (H) and the generation of leukotrienes (LT) from nearby mast cells. These mediators then produce vasodilatation and an increase in vascular permeability. In addition, they act on the nerve terminal to produce further...

Neurotensin (NT) is a tridecapeptide (Table 4.2) first isolated from brain and gut by Carraway and Leeman [75] and reported by them to induce a rapid and transient hypotension, a cutaneous vasodilatation, and a cyanosis of the extremities in the anaesthetized rat. This report, along with others [76-78] indicating that the NT-induced hypotension and increased vascular permeability could be blocked by histamine receptor antagonists such as mepy-ramine [77] or by pretreatment with compound 48/80 [76], suggested that endogenous histamine (perhaps released from tissue mast cells) was involved in producing some of the biological effects of NT [78]. 

Figure 4.8. Hypothesis for the local generation of mast-cell-stimulating peptides by the action of neutrophil-derived enzymes on albumin. Initial stimulation of the mast cell by any of a variety of agents causes the release of preformed histamine (H) neutrophil and eosinophil chemotactic factors (NCF, ECF) and enzymes and the de novo synthesis of prostaglandins (PG) and leukotrienes (LT). These agents increase vascular permeability and vessel diameter. As a result, albumin and later neutrophils (PMN) enter the tissue space where the latter undergo phagocytosis and the secretion of proteolytic enzymes to the extracellular space where they act on albumin to generate NRP (neurotensin-related peptide) and HRP (histamine-releasing peptide). These newly formed peptides then act as a second stimulus to the mast cell. In addition NRP and HRP may affect other immunocompetent celt such as monocytes, macrophages or eosinophils.

Histamine Mast cells, basophils Contraction of smooth muscle increases vascular permeability... 

Histamine Hr Human cDNA Allergy inflammation, asthma, chronic sinusitis, rhinitis, epilepsy migraine, motion sickness, pain, cancer Smooth muscle contraction, increase in vascular permeability stimulation of hormone release (adrenal medulla), increase in neuronal firing... 

Mechanism of Action A mast cell stabilizer that prevents increase in cutaneous vascular permeability, antigen-stimulated histamine release, and may prevent calcium influx into mast cells. Therapeutic Effect Inhibits sensitivity reaction. Pharmacokinetics Nondetectable absorption. Half-life 8.5 hr. 

Apart from histamine, leukotiienes liberated during inflammation are more powerful bronchoconstrictor and longer acting. Leukotrienes also increase bronchial mucus secretion and increase vascular permeability. All the leukotrienes are derived from 5-lipoxygenase pathway of arachidonic acid and are synthesized by a variety of inflammatory cells in the airways e.g. eosinophils, mast cells, basophils and macrophages. The LTB, exert many... 

Antiinflammatory effects of astramembrannin I (astragaloside IV), isolated from A. membranaceus, were demonstrated in rats. This compound inhibited the increase of vascular permeability induced by serotonin or histamine. Oral administration of astramembrannin I caused a dose dependent reduction in carrageenan-induced edema of the hind paw of rats [15]. 

The Hi Receptor and its ligands. The 11, receptor mediates most uf the important histamine effects in allergic diseases. These include smooth muscle contraclion. increased vascular permeability, pruritus, prostaglandin generation, decreased atrioventricular node conduction time with resultant tachycardia, activation of vagal reflexes, and increased cyclic guant sine monophosphate tcGMP) production. 

Much like what was described in heart and lung, neuropeptides may release histamine from mast cells, which in turn may act on presynaptic H3-receptors (Matsubara et al., 1992). In this regard, endogenous histamine exerts a two faceted influence on neurogenic inflammation, since this substance may also cause vasodilatation and rise in vascular permeability through the Hi-receptor/NO-pathway (Levi et al., 1991 Lassen et al., 1995). 

In this regard, endothelial histamine H3 receptors closely resemble the Hi-subtype, which is known to operate with a similar mechanism on the resistance vessels to produce vasodilatation, increased vascular permeability and hypotensive effects, by way of a mechanism... 

Palitzsch, K.D., Horales, R.E., Kronauge, J.F., Szabo, S., 1989. Biphasic effect of histamine on hemorrhagic mucosal lesions is related to vascular permeability studies with histamine, Hi-, H2- and H3-agonists and bradykinin. Gastroenterology 96, (Suppl.) A381. 

Neutrophils are also rapidly attracted to the site of a foreign body reaction, but likely persist in large numbers for only a few days. They generally reside within blood vessels, but in response to signals such as histamine, which increases vascular permeability, neutrophils enter the extravascular space through a process known as diapedesis. A recent study by Wozniak found that nitric oxide produced by neutrophils plays an important role in loosening of total joint implants.11... 

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