Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bovine splenic nerve trunk contains mast cells, ganglion cells, small intensely fluorescent (SIF) cells, and varicosities which exhibit a brilliant fluorescence characteristic for noradrenaline (NA) and dopamine (DA) after formaldehyde exposure. All these catecholamine-rich structures could contribute particles to isolated nerve vesicle fractions. Mast cells are recognized ultrastructurally by their large (300-800 nm) dense granules. SIF cells may be represented by cells and processes containing dense cored vesicles (120-140 nm) which are larger than the typical vesicles in axons and terminals. Terminal-like areas with typical large dense cored vesicles (LDV, 75 nm) and small dense cored vesicles (SDV, 45-55 nm) probably correspond to the fluorescent varicosities. The LDV constitute about 40% of all vesicles in terminal-like areas and terminals. Their staining properties indicate the presence of protein, phospholipids, and ATP. Tyramine depletes NA without loss of matrix density. The LDV can fuse with the terminal membrane, and released material outside omega profiles is interpreted to depict exocytosis. Large and small vesicles are easily distinguished from the very large mast cell granules and the moderately dense Schwann cell vesicles. Neither appear to contaminate the LDV fractions but the latter may contain a small population of SIF cell vesicles. Golgi vesicles from the Schwann cells mainly occur in the lighter zones of the gradient.
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PMID:Catecholamine-rich cells and varicosities in bovine splenic nerve, vesicle contents and evidence for exocytosis. 45 41

Calcitonin gene-related peptide (CGRP) is known to block Con A and PHA induced T cell proliferation. As a first step in determining the role of this peptide in T cell education and function we have studied the distribution of CGRP within the developing mouse thymus using immunocytochemistry. CGRP-like immunoreactivity (CGRP-IR) was found in the thymic nerves in close proximity to blood vessels in the 17-day-old embryonic mouse thymus. A discrete population of small cells at the cortico-medullary junction also stained intensely for CGRP. As the mouse thymus reached maturity (three to eight weeks) CGRP innervation became more dense, with fibers running along the vasculature at the cortico-medullary boundary, then branching into the cortical and medullary regions. Some fibers were invested in the blood vessels while a large portion formed varicosities among the cells of the thymus. In the mature thymus, the small CGRP-IR cortico-medullary cells were more numerous, and CGRP-IR was also found in subcapsular and trabecular mast cells. The pattern of innervation remained the same in the aging mouse thymus (six months), but there appeared to be somewhat fewer cortico-medullary cells and an increase in mast cell number. In the aged (eighteen months) thymus, the small CGRP-IR cortico-medullary cells were rarely seen, but mast cells were more numerous, most of which stained positively for CGRP, in the connective tissue. Nerves containing CGRP-IR generally had the same distribution as in the younger mice but appeared somewhat truncated. The distribution of CGRP-IR nerves in the mouse thymus at different stages of development was similar to that reported for cholinergic (AChE-positive) nerves. Since the brain-stem vagal nuclei have been shown by retrograde transport studies to project to the thymus as well as to contain CGRP-IR neurons, our findings suggest that CGRP-IR thymic nerves may be derived from the vagus complex.
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PMID:Calcitonin gene-related peptide in the developing and aging thymus. An immunocytochemical study. 185 88

Fluorescent and acetylcholinesterase-positive cell bodies occur in the connective tissue surrounding the prostatic end of the monkey vas deferens. At both the testicular and prostatic ends, noradrenergic nerve fibres are distributed mainly in the smooth muscle coats while acetylcholinesterase-positive fibres are most densely distributed in the lamina propria but also quite significantly in the inner part of the smooth musculature. The percentage of cholinergic varicosities (containing a predominance of small agranular vesicles and some large granular vesicles) is higher in the smooth muscle coat than in the lamina propria at both the testicular (9.1% against 1.5%) and prostatic (19.38% against 5.16%) ends of the vas deferens and the percentages of cholinergic varicosities in both the lamina propria and smooth muscle coat (5.16% and 19.38% respectively) at the prostatic end are higher than those (1.5% and 9.1% respectively) at the testicular end. The percentage of noradrenergic varicosities (containing a predominance of small granular vesicles interspersed with some large granular vesicles and agranular vesicles) in the muscle coat is higher at the testicular (56.72%) than the prostatic (39.73%) end. In addition to cholinergic and noradrenergic nerves, varicosities resembling purinergic nerve fibres, varicosities containing flattened vesicles and sensory terminals are also present. In nearly all cases where no collagen fibres intervene between an axon varicosity and the smooth muscle membrane, the interval between the two is less than 180 nm, and may be as little as, or even less than, 20 nm. Lastly, close nerve-mast cell and nerve-fibroblast contacts have been observed.
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PMID:Innervation of the monkey vas deferens. 208 13

By histofluorescence microscopic examinations of pial arteries from rats and rabbits, we have observed that the routes of adrenergic fibers were apparently organized along successive sites of granular autofluorescent cells present in the adventitia. Subsequent electron microscopic studies showed that these cells were often situated in close apposition (80 to 200 nm) to the adventitial nerve bundles. The granular cells and nerve varicosities were frequently enclosed within the same basement membrane, with a membrane-to-membrane distance as small as 20 nm. However, no clear membrane differentiation was seen. These granular cells were identified histochemically by staining with Sudan Black, Oil Red O, Toluidine Blue, Alcian Blue, together with ultrastructural and pharmacological methods (48/80 compound and carbachol intracarotid infusions). The cells, many of which contained large amounts of lipids, showed morphological ultrastructural and pharmacological similarities to peripheral mast cells. Nerve bundles contained two types of varicosities: some of them degenerated after superior cervical ganglionectomy and were thus of sympathetic origin, whereas the others contained small clear vesicles (probably cholinergic) and/or large dense-cored vesicles (probably peptidergic). As we have shown that cholinomimetics induce exocytosis of these granular cells, the close relationship between these cells and the nerve fibers may indicate a neurogenic control of the cerebrovascular mast cell secretion. As these cells contain potent vasoactive substances, this relationship may be of importance in the genesis of physiological or pathological cerebrovascular events which are, as yet, poorly understood.
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PMID:Ultrastructural evidence for a functional unit between nerve fibers and type II cerebral mast cells in the cerebral vascular wall. 367 Jun 1

The epithelium of the gastrointestinal tract is continuously exposed to the external environment containing food antigens, microbes and other pathogens. Immunologic and nonimmunologic mechanisms contribute to the neutralization and elimination of these foreign antigens. The immune system of the intestine is the most extensive in the organism and involves diffuse populations of immune cells, lymphoid aggregates and intraepithelial lymphocytes. On the other hand, the functions of the digestive tract contribute to the overall host defense (mucus secretion, gastric acid secretion, water and electrolyte secretion and peristaltism). These functions are regulated by intrinsic and extrinsic nervous systems. It is currently recognized that the physiological and pathological responses of the intestine require an integrate neuroimmune network. Such neuroimmune regulation is based on anatomical and biochemical supports. Indeed, there are membrane-to-membrane contacts between axonal varicosities and the immune cells. Specific receptors for neurotransmitters such as substance P, vasoactive intestinal polypeptide and somatostatin have been identified in many immune cells. Nerve profile change has been described under pathological conditions such as parasitic infections and acute phase of inflammation. In addition to supporting the growth and survival of several populations of nerves the classical nerve growth factor (NGF) has been shown to affect an immune cell population by inducing mast cell hyperplasia. Furthermore the NGF can induce mast cell degranulation, acting directly on mast cell membrane NGF receptors or indirectly by NGF-mediated release of substance P by peripheral extrinsic or intrinsic nerves. Moreover, non-immune cells such as epithelial and smooth muscle cells can produce immunologic messengers under pathological conditions such as infectious diseases or inflammation. Besides the local regulation of gut functions, neuroimmune control can be exerted at extra-intestinal sites. During physiological and pathological conditions, gastrointestinal secretions and motor events are strongly regulated by the central nervous system. Moreover, infectious agents can induce cytokine and particularly interleukin-1 release by the brain astrocytes and microglial cells which have been shown to play a pivotal role in fever induction and modifications of the gastrointestinal functions. Visceral afferent fibers play a pivotal role in 'cross-communication' between central sites and immune response. Recent studies evoke, more specifically, the role of vagus as a key modulatory participant in the close relationship between the extraintestinal nerves and the immune system. Future work in this field will clarify the role of the different participants in the intimate communication between the gastrointestinal tract, immune system and central nervous system.
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PMID:Integrative neuroimmunology of the digestive tract. 882 13

Cutaneous antidromic vasodilatation and plasma extravasation, two phenomena that occur in neurogenic inflammation, are partially blocked by substance P (SP) receptor antagonists and are known to be mediated in part by mast cell-released substances, such as histamine, serotonin, and nitric oxide. In an attempt to provide a morphological substrate for the above phenomena, we applied light and electron microscopic immunocytochemistry to investigate the pattern of SP innervation of blood vessels and its relationship to mast cells in the skin of the rat lower lip. Furthermore, we examined the distribution of SP (neurokinin-1) receptors and their relationship to SP-immunoreactive (IR) fibers. Our results confirmed that SP-IR fibers are found in cutaneous nerves and that terminal branches are observed around blood vessels and penetrating the epidermis. SP-IR fibers also innervated hair follicles and sebaceous glands. At the ultrastructural level, SP-IR varicosities were observed adjacent to arterioles, capillaries, venules, and mast cells. The varicosities possessed both dense core vesicles and agranular synaptic vesicles. We quantified the distance between SP-IR varicosities and blood vessel endothelial cells. SP-IR terminals were located within 0.23-5.99 microm from the endothelial cell layer in 82.7% of arterioles, in 90.2% of capillaries, and in 86.9% of venules. Although there was a trend for SP-IR fibers to be located closer to the endothelium of venules, this difference was not significant. Neurokinin-1 receptor (NK-1r) immunoreactivity was most abundant in the upper dermis and was associated with the wall of blood vessels. NK-1r were located in equal amounts on the walls of arterioles, capillaries, and venules that were innervated by SP-IR fibers. The present results favor the concept of a participation of SP in cutaneous neurogenic vasodilatation and plasma extravasation both by an action on blood vessels after binding to the NK-1r and by causing the release of substances from mast cells after diffusion through the connective tissue.
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PMID:Light and electron microscopic study of the distribution of substance P-immunoreactive fibers and neurokinin-1 receptors in the skin of the rat lower lip. 1126 9

Varicose veins of the lower extremities are abnormally dilated, tortuous and elongated. The exact cause of vein dilatation has still not been established. Mast cells produce, store and release various types of vasoactive compounds (histamine, tryptase, prostaglandins, leukotrienes, and cytokines). Histamine enhances local vasopermeability and smooth muscle cell proliferation, leading to thickening of the intima. Tryptase can contribute to local vascular injury and subsequent weakness of the vascular wall causing varix formation. The aim of the present study was the comparison of mast cell infiltration in the wall of varicose and non-varicose veins. The mean mast cell density in the wall of varicose veins was 0.86 mast cell per mm2 and in healthy non-dilated vein walls, density was 1.23 mast cell per mm2. This difference was not statistically significant, therefore we could not confirm our hypothesis. Nevertheless, we suggest that mast cells could play an important role in the development of varices and the factor released by the mast cells should be further examined.
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PMID:Mast cell infiltration in the wall of varicose veins. 1255 2

The colocalization of histamine (HA) and norepinephrine (NE) immunoreactivities was identified within the superior cervical ganglia neurons of the guinea pig. HA and NE immunoreactivity levels were significantly attenuated after chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Coexistence of NE and HA was also visualized in the cardiac sympathetic axon and varicosities labeled with anterograde tracer biotinylated dextran amine. Depolarization of cardiac sympathetic nerve endings (synaptosomes) with 50 mM potassium stimulated endogenous HA release, which was significantly attenuated by 6-OHDA or a vesicular monoamine transporter 2 (VMAT2) inhibitor reserpine pretreatments. Compound 48/80, a mast cell releaser, did not affect cardiac synaptosome HA exocytosis. Furthermore, K+ -evoked HA release was abolished by the N-type Ca2+ -channel blocker omega-conotoxin but was not affected by the L-type Ca2+ -channel blocker lacidipine. Cardiac synaptosome HA exocytosis was augmented by the enhanced synthesis of HA or the inhibition of HA metabolism. HA H3-receptor activation by (R)-alpha-methylhistamine inhibited high K+ -evoked histamine release. The HA H3 receptor antagonist thioperamide enhanced K+ -evoked HA release and blocked the (R)-alpha-methylhistamine effect. The K+ -evoked endogenous NE release was attenuated by preloading the cardiac synaptosomes with L-histidine or quinacrine. These inhibitory effects were reversed by thioperamide or antagonized by alpha-fluoromethylhistidine. Our findings indicate that high K+ -evoked corelease of NE and HA may be inhibited by endogenous HA via activation of presynaptic HA H3-receptors. The H3-receptor may function as an autoreceptor, rather than a heteroreceptor, in the regulation of sympathetic neurotransmission and HA may be a novel sympathetic neurotransmitter.
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PMID:Evidence for histamine as a neurotransmitter in the cardiac sympathetic nervous system. 1639 66

Pain intensity in chronic venous disease varies with the stage in the clinical-etiologic-anatomic-pathophysiologic (CEAP) classification but also with patient perception, pain being by definition subjective. The venous hypertension responsible for the varicose veins and trophic changes in CVD has a variety of algogenic repercussions in which leukocytes play a particular role, notably through their ability to roll along the vessel wall. Shear stress, hypoxia and stasis activate the marginated leukocytes to shed L-selectin from their surface and express integrins, matrix metalloproteinase 9, elastase, lactoferrin and free radicals. Meanwhile the endothelium expresses adhesion molecules that permit slow rolling on E-selectin followed by adhesion and tissue transmigration. Vein wall and valve areas in particular attract mast cells, monocyte-macrophages and T lymphocytes, and undergo remodeling. Sympathetic sensory C and Adelta fibers, which wrap around cutaneous venules and are also present in the venous intima and media, are nociceptors sensitive to the pain mediators concentrated within leukocytes, such as mast cell bradykinin, responsible for visceral pain. Neuronal inflammation combined with wall remodeling intensifies symptoms. Yet no direct link has so far been shown between pain and mast cell mediator levels. Leukocyte adhesion is also associated with the increased capillary permeability that leads to edema. Antileukocyte therapies include postural rest and venotonics which alone or in combination with compression have been shown to unstick and inhibit leukocytes. The micronized purified flavonoid fraction (MPFF) protects vascular endothelium against hypoxia and reduces adhesion molecule expression. Unlike other antileukocyte therapies, venotonics do not cause neutropenia.
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PMID:Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. 1772 58