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 norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat is preceded by increased interleukin (IL)-6 expression and associated with LV fibrosis. We have examined whether the elevated level of IL-6 may be due to mast cell degranulation. Therefore we tested the effect of cromoglycate sodium salt (cromolyn), an inhibitor of mast cell degranulation with anti-inflammatory and membrane-stabilizing activity, on the increased expression of IL-6 mRNA and of mRNAs of proteins involved in the remodelling of the extracellular matrix (ECM) which is induced by NE (0.1 mg/kg x h). After 4 h, the NE-induced increase in IL-6 mRNA expression was not influenced by cromolyn (20 mg/kg x h). Cromolyn-infusion for 3 days did not affect the extent of LV hypertrophy induced by NE, as measured by the LV weight/body weight (LVW/BW) ratio and by atrial natriuretic peptide (ANP) expression. Cromolyn induced a slight depression of the NE-induced elevation of the matrix metalloproteinase (MMP)-2. However, it did not affect the NE-induced elevated levels of mRNAs of collagen I and III and the tissue inhibitor of matrix metalloproteinase (TIMP)-2. Since cromolyn did not reduce the NE-effects in rat hearts in vivo we conclude that mast cell degranulation seems not to be involved in them.
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PMID:Norepinephrine-induced cardiac hypertrophy and fibrosis are not due to mast cell degranulation. 1457 97

Eosinophilic colitis is a rare entity of unknown etiology characterized by diarrhea, abdominal pain, and gastrointestinal bleeding. Diagnosis includes histopathological infiltration of more than 20 eosinophils in colon. It is frequently associated with milk hypersensitivity and, less usual, with other foods and increased IgE. Histopthological appearance of eosinophil mediators has been observed in the gut. It is sometimes related to the degree of infiltration of eosinophils in the gut as well as to the disease severity. There is not an established treatment for this entity, although systemic steroids have been used with certain efficacy. However, there is a recurrence of the symptoms when the therapy stops, besides the well known side effects of the long-term use of steroids. Cromolyn inhibits mast cell degranulation and prevents liberation of mediators. It is successful in certain cases, specially the severe ones. However, it is not available for its use in our country. Ketotifen, as last resource in our patients with bad response to habitual treatment and restriction diet, was used. Although its use is controversial, we consider that stabilizing mast cell membrane with subsequent inhibition of degranulation and recruitment of eosinophils to sites of inflammation, would also restrain histamine liberation and blockage of H1 receptors, which would diminish local damage induced by eosinophils. Nonetheless ketotifen mechanism of action is unknown, our patients improved after treatment with this drug.
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PMID:[Eosinophilic colitis. A report of two cases with non conventional treatment]. 1579 16

Airway hyper-reactivity to inhaled adenosine, mediated via mast cell activation, is a cardinal feature of asthma. Animal models have been developed in several species to mimic this phenomenon, but only in the rat has a mast cell involvement been clearly defined. In this study, a model of ovalbumin-induced adenosine hyper-reactivity was developed in BALB/c mice to determine whether mast cells are involved in this phenomenon. Sensitised mice were challenged one, two or three times, on a daily basis, and airway responses to the stable adenosine analogue NECA (5'-N-ethylcarboxamido adenosine) determined 4 and 24 h after each challenge. Airway hyper-reactivity was observed in ovalbumin-challenged mice 4 h after a single challenge and to a minor extent 24 h after a single challenge and 4 h after two challenges. Cromolyn (20 mg ml(-1)), given by aerosol an hour before the NECA provocation, fully inhibited the airway hyper-reactivity observed 4 h after a single allergen challenge, suggesting a role for mast cells in this response. The airway space cellular inflammation was not affected by cromolyn. As observed in human asthma, an acute treatment with steroid (budesonide 3 mg kg(-1), given an hour before the allergen challenge) inhibited the NECA airway hyper-reactivity and significantly inhibited the airway space cellular inflammation. These data suggest that the ovalbumin-challenged BALB/c mice can be considered as a suitable model to study the adenosine-induced airway hyper-reactivity phenomenon observed in human asthma.
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PMID:Mast cell involvement in the adenosine mediated airway hyper-reactivity in a murine model of ovalbumin-induced lung inflammation. 1591 30

Pancreatitis-associated lung injury is an early-occurring and severe complication, still associated with substantial mortality. A number of inflammatory cells and their products are involved in the initiation and progress of the condition. In the present study, acute pancreatitis (AP) was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Pulmonary endothelial barrier dysfunction was measured by plasma exudation of radiolabeled albumin. Expression of PECAM-1, ICAM-1, and L: -selectin on neutrophils (CD11b(+)) and monocytes/macrophages (CD11b/c(+)), obtained from circulation and lung tissue, was measured 1 and 6 hours after AP induction (n = 10 rats/time point/group). Plasma levels of histamine and serotonin were determined. The role of mast cells was evaluated by pretreatment with the mast cell stabilizer cromolyn. Intraperitoneal administration of cromolyn downregulated pancreatitis-induced systemic increase of histamine at 1 hour (513 +/- 82 vs. 309 +/- 50, p < 0.05). Cromolyn prevented a decreased expression of PECAM-1 on circulatory neutrophils and monocytes/macrophages and against an increased expression of ICAM-1 and PECAM-1 on pulmonary neutrophils and monocytes/macrophages 6 hours after AP induction (about 40% vs. 10%, p < 0.01). The mast cell stabilizer also prevented pancreatitis-induced pulmonary endothelial barrier dysfunction at 6 hours. Thus, our data indicate that mast cells may play a critical role in the activation of leukocytes during the initiation of pancreatitis-associated lung injury by altering phenotypes of adhesion molecules.
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PMID:Influence of mast cells on the expression of adhesion molecules on circulating and migrating leukocytes in acute pancreatitis-associated lung injury. 1621 61

Nociceptin/orphanin FQ (N/OFQ) is an opioid-like neuropeptide that has been shown to cause peripheral sensitization of knee joint afferents; however, the effect of the peptide on joint pain behaviour is unknown. In addition to having a direct effect on peripheral nerves, N/OFQ has also been shown to activate connective tissue mast cells causing the local release of potentially pain causing mediators. The present study tested the effect of peripherally administered N/OFQ on joint pain and examined whether synovial mast cells contribute to these responses. Hindlimb weight bearing and von Frey hair algesiometry were measured before and following a single injection of N/OFQ in the vicinity of the right knee of male Wistar rats. Compared to saline-treated controls, N/OFQ caused a conspicuous shift in hindlimb weight bearing in favour of the contralateral non-injected leg. Similarly, paw withdrawal threshold and latency were significantly reduced following N/OFQ administration indicative of secondary hyperalgesia. To test the involvement of synovial mast cells in these pain reactions, a separate group of rats were treated with the mast cell stabilizer cromolyn (20 mg/kg s.c.) 5 min prior to N/OFQ injection. Cromolyn treatment had no significant effect on N/OFQ-induced weight bearing deficit nor secondary hyperalgesic responses. In conclusion, these data support the premise that N/OFQ has a pain causing effect in the periphery which occurs independently of mast cell activation.
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PMID:Nociceptin/orphanin FQ evokes knee joint pain in rats via a mast cell independent mechanism. 1642 60

Mast cells are located in the mammalian thalamus where their numbers are sensitive to reproductive hormones. To evaluate whether differences between sexes and over the estrus cycle influence the nuclear distribution of mast cells in mice, we mounted a comprehensive analysis of their distribution in males compared to females and in females over the estrus cycle. Compared to males, mast cells were more numerous in the lateral intralaminar and posterior nuclei of females during estrus and in the ventral posterolateral (VPL) and medial geniculate nuclei during proestrus. During estrus, mast cells were especially concentrated in those regions within the VPL and posterior thalamic nuclei that receive somatosensory information from the anogenital region. Treatment of ovariectomized mice with estrogen increased the number and the percent of mast cells that were degranulated compared to that after ovariectomy alone, an effect that was most apparent in the lateral intralaminar, VPL and posterior nuclei. In estrogen-primed, ovariectomized females, progesterone delivered 5 h before tissue collection counteracted the effects of estrogen. Cromolyn, a mast cell stabilizer, injected centrally 1 h prior to and 24 h after estrogen in ovariectomized mice, prevented the increase in number of mast cells in the whole thalamus and in the intralaminar, VPL and posterior nuclei. This suggests that estrogen induces hyperplasia by a mechanism that involves mast cell degranulation. Based on the discrete anatomical location of mast cells in areas of somatosensory nuclei that receive anogenital input together with the temporal correspondence of these cells with estrus, mast cells are well situated to influence sensory input in females during mating.
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PMID:Mast cells accumulate in the anogenital region of somatosensory thalamic nuclei during estrus in female mice. 1694 55

Although many authors have considered a direct interaction between allergic reactions and behavioral changes, supporting evidence has been elusive. In this series of studies we show that after oral or nasal ovalbumin (OVA) challenge, allergic mice present increased Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA). Mice with food allergy display higher levels of anxiety and increased serum corticosterone levels, and allergy-activated neurons express corticotropin-releasing factor (CRF) in the PVN and CeA. OVA-allergic mice develop aversion to an antigen-containing solution, and also avoid a dark compartment previously associated with nebulized OVA. Results on brain Fos expression and behavioral data seem compatible with adaptive responses. Removal of IgE by either antibody depletion or the development of oral tolerance precluded all responses analyzed here. C-sensitive fiber destruction by neonatal capsaicin inhibited the activation in the PVN, but not in the CeA, and decreased the magnitude of food aversion. Cromolyn, a mast cell stabilizer, completely blocked Fos expression in the PVN and CeA, and precluded the development of aversion to the dark compartment associated with nebulized OVA. Employing mice that do not develop an important inflammatory infiltrate following nasal OVA challenge, we found that inflammatory cells are not required at the site of challenge in order to trigger neural or behavioral correlates of murine experimental asthma. Altogether, we have built a solid foundation for understanding neuroimmune interactions during allergic responses that may contribute to the comprehension of psychological disorders associated with allergy.
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PMID:Neural correlates of IgE-mediated allergy. 1719 60

Experimental airway allergy in mice leads to increased activity in specific hypothalamic and amygdaloid nuclei, and behavioral changes. The experiments described here were designed to determine the role of anaphylactic antibodies, mast cell degranulation, and lung inflammation in the neural and behavioral correlates of an experimental murine asthma-like response. Animals were sensitized intraperitoneally with ovalbumin adsorbed to alum, and challenged by intranasal ovalbumin instillation or aerosol. To induce immunological tolerance, animals were fed ovalbumin in the drinking water for 5 consecutive days, along with primary sensitization. Depletion of IgE was also accomplished with a non-anaphylactic anti-IgE antibody. Mast cell degranulation was inhibited by cromolyn. In addition to BALB/c animals, C3H/HeJ mice were used for their relative resistance to lung allergic inflammation. We confirmed that ovalbumin challenge in allergic mice leads to increased activity in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and avoidance behavior towards an allergen-associated compartment. Moreover, these responses were precluded by oral tolerance or anti-IgE treatment, even in the presence of IgG1. Cromolyn abrogates both responses in the presence of anaphylactic antibodies. Finally, although sensitized C3H/HeJ mice did not develop airway inflammation, they exhibited brain and behavioral changes similar to BALB/c animals. The repercussions of murine allergic asthma on brain and behavior are IgE-dependent, mediated by mast cell degranulation, and do not require a pulmonary inflammatory infiltrate, suggesting that the early phase of this immediate allergic response suffices for the brain activation associated with avoidance behavior towards exposure to the allergen.
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PMID:Role of mast cell degranulation in the neural correlates of the immediate allergic reaction in a murine model of asthma. 1729 17

The objective of this study is to investigate the effect of a mast cell degranulating agent, compound 48/80, on vascular resistance in the perfused human placenta and on the tone of isolated human chorionic vessels. Human placenta was obtained from term nonlaboring women undergoing cesarean delivery. Placental vascular bed perfusion pressure and isometric tension for segments of chorionic plate artery and vein were obtained in response to potassium chloride, compound 48/80, a mast cell stabilizer (cromolyn), and thromboxane A2 mimetic (U46619). Compound 48/80 significantly increased perfusion pressure in isolated human placental cotyledons. This effect was significantly potentiated further after induction of active vascular tone by thromboxane A2 mimetic U46619. Cromolyn significantly attenuated responses to compound 48/80 in these preparations. Compound 48/80 also significantly increased tone in isolated human chorionic artery and vein rings, and responses were abolished by cromolyn. In conclusion, degranulation of placental and intravascular mast cells by compound 48/80 leads to the release of vasoconstrictive substances. This could impair placental blood flow and result in growth restriction in fetuses of women with type l hypersensitivity reactions.
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PMID:The effect of a mast cell degranulating agent on vascular resistance in the human placental vascular bed and on the tone of isolated placental vessels. 1821 51

Premature infants are at increased risk of developing airway hyper-reactivity (AHR) after oxidative stress and inflammation. Mast cells contribute to AHR partly by mediator release, so we sought to determine whether blocking mast cell degranulation or recruitment prevents hyperoxia-induced AHR, mast cell accumulation, and airway smooth muscle (ASM) changes. Rats were exposed at birth to air or 60% O2 for 14 d, inducing significantly increased AHR in the latter group, induced by nebulized methacholine challenge and measured by forced oscillometry. Daily treatment (postnatal d 1-14) with intraperitoneal cromolyn prevented hyperoxia-induced AHR, as did treatment with imatinib on postnatal d 5-14, compared with vehicle treated controls. Cromolyn prevented mast cell degranulation in the trachea but not hilar airways and blocked mast cell accumulation in the hilar airways. Imatinib treatment completely blocked mast cell accumulation in tracheal/hilar airway tissues. Hyperoxia-induced AHR in neonatal rats is mediated, at least in part, via the mast cell.
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PMID:Mast cells mediate hyperoxia-induced airway hyper-reactivity in newborn rats. 2578 Aug 66


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