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

Tryptase and chymase released from activated mast cells degrade the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) to peptide fragments. We have examined whether nedocromil sodium can modulate the ability of rat activated peritoneal mast cells to degrade 125I-CGRP and 125I-VIP. Mast cell-dependent degradation of both 125I-CGRP and 125I-VIP was observed with compound 48/80 (0.03-1 microgram/ml) and in the case of 125I-VIP with anti-IgE (1-20 micrograms/ml). Nedocromil sodium (10(-6)-10(-4) M) caused significant inhibition of neuropeptide degradation, with the most effective inhibition observed against anti-IgE-induced degradation of 125I-VIP. Nedocromil sodium had no inhibitory effect on the ability of lysed mast cells, bovine trypsin or chymotrypsin to breakdown 125I-VIP. These results suggest that nedocromil sodium inhibits mast cell-dependent degradation of neuropeptides, such as VIP, as a secondary consequence of inhibiting the release of mast cell proteases.
 ...
PMID:The modulation by nedocromil sodium of proteases released from rat peritoneal mast cells capable of degrading vasoactive intestinal peptide and calcitonin gene-related peptide. 839 43

The proteolytic cleavage product of complement component 3, (C3a), is like C4a and C5a, is a potent anaphylatoxin and induces the production of inflammatory mediators in phagocytes. Notably, mast cells respond to C3a with the release of vasoactive substances, including histamine. We have examined the function and receptor binding of C3a in a human leukemic mast cell line, HMC-1. Similar to chemoattractant agonists in leukocytes, C3a induced rapid cytosolic free calcium concentration increases in HMC-1 cells. EGTA did not diminish this response, indicating that mobilizable Ca2+ was from intracellular stores. Receptors of C3a in HMC-1 cells couple in part to Bordetella pertussis toxin-sensitive G-proteins and, therefore, appear to belong to the family of serpentine receptors that require G-proteins for signal transduction. HMC-1 cells express two types of C3a receptors, C3aR1 and C3aR2, that were shown to bind 125I-C3a with high-(Kd1 = 2.1-4.8 nM) or low-affinity (Kd2 = 30-150 nM), and both receptors are expressed at high level: 3 x 10(5)-6 x 10(5) C3aR1/cell and 5 x 10(5)-2.3 x 10(6) C3aR2/cell. Results from cross-linking experiments with 125I-C3a fully agree with the presence of two different classes of C3a receptors in HMC-1 cells. Two membrane proteins with apparent molecular masses of 54-61 kDa (p57) and 86-107 kDa (p97) could be covalently modified with 125I-C3a, and this cross-linking was inhibited with an excess of unlabeled C3a. Many of the known agonists for leukocytes including 13 chemokines (IL-8, NAP-2, GRO alpha, ENA-78, IP10, PF4, MCP-1, 2 and 3, RANTES, MIP-1 alpha, MIP-1 beta and I309), three neuropeptides (neuropeptide Y, somatostatin and calcitonin), as well as C5a, did not activate HMC-1 cells, indicating that C3a is one of a few protein ligands for which this cell line expresses specific receptors. The apparent selectivity for C3a and the abundant expression of C3a receptors make the HMC-1 cell line an excellent choice for the cloning of the receptor genes.
 ...
PMID:Expression of high- and low-affinity receptors for C3a on the human mast cell line, HMC-1. 862 64

Urinary bladders of normal adult female guinea pigs were analyzed for anatomical evidence of nerve-mast cell interaction using light microscopy and electron microscopy. Nerves, ganglia, and individual nerve fibers were visualized on paraffin sections using immunohistochemistry with antisera against the neural antigens neurofilament protein and protein gene product 9.5, and sections were also immunoreacted with antisera against the neuropeptides substance P and calcitonin gene-related peptide. Separate mast cell populations were identified by counterstaining with toluidine blue and alcian blue. Mast cells of both types were found within nerves and intramural ganglia and were in close contact with individual nerve fibers displaying substance P- and calcitonin gene-related peptide-like immunoreactivity. Moreover, serotonin-immunoreactive mast cells were innervated with nerve fibers that reacted with antiserum against vasoactive intestinal polypeptide. At the ultrastructural level, these fibers were almost exclusively identified as unmyelinated primary sensory afferents. Mast cells contacted these fibers with lamellipodia that wrapped around and enclosed the fibers deeply within the cell. Close association between mast cells, nerves, and vessels was common. Ultrastructural evidence suggests that bidirectional communication occurs between nerve fibers and mast cells. These structures may participate in axon reflexes that regulate normal vascular and detrusor smooth muscle function and cause vasodilation, edema, inflammation, and bladder hyperreactivity. In summary, a close relationship exists between mast cells and peptidergic nerve fibers, including primary sensory afferents. Results suggest that bidirectional interaction could occur between nerves and mast cells.
 ...
PMID:Nerve-mast cell interaction in normal guinea pig urinary bladder. 868 35

Nerve growth factor (NGF) is known to produce hyperalgesia as well as to stimulate synthesis of neuropeptides in dorsal root ganglia (DRG). In the present study, we wanted to determine the effects of local NGF administration and assess to which extent mast cell-dependent factors are mediating NGF responses. Rats received 1 daily unilateral intraplantar injection for 3 days. Local edema (days 1-3), changes in thermal nociceptive threshold (days 1-4), and the content of calcitonin gene-related peptide (CGRP) and substance P (SP) in the sciatic nerve (day 4), were determined. NGF injection caused edema which was absent in rats pretreated with compound 48/80 as well as in rats treated neonatally with capsaicin ('capsaicin denervation'). NGF-induced edema was not reduced by the neurokinin-1 receptor antagonist SR140333, but attenuated by the CGRP receptor antagonist CGRP[8-37]. On each day, NGF injection caused a decrease in thermal nociceptive threshold which lasted for less than 3 h. Capsaicin denervation, but not treatment with indomethacin, abolished NGF-induced thermal hyperalgesia. Treatment with compound 48/80 attenuated hyperalgesia produced by the first, but not by subsequent, NGF injections. On day 4, 24 h after the last of 3 NGF injections, thermal nociceptive threshold was not different from control values, but at that time, CGRP and SP were elevated in the sciatic nerve. We suggest therefore that NGF-induced local edema was caused by mast cell-derived vasoactive compounds which act together with afferent neuron-derived CGRP to increase vascular permeability. NGF-induced thermal hyperalgesia most likely was caused by an increased sensitivity of peripheral endings of capsaicin sensitive afferents. This effect of NGF was not mediated by products of the cyclooxygenase pathway, and was also observed in mast cell-depleted rats.
 ...
PMID:Intraplantar injection of nerve growth factor into the rat hind paw: local edema and effects on thermal nociceptive threshold. 874 Jun 10

The first week of dietary magnesium deficiency in rodent models is characterized by the induction of raised levels of neuropeptides (substance P [SP] and calcitonin gene related peptide [CGRP]), followed shortly thereafter by inflammatory cytokine release. Since neuropeptides participate in neurogenic inflammation, we have proposed that the neurogenic inflammatory response plays a role in the pathology of magnesium deficiency. However, the association between the early neuropeptide release and the subsequent pathology in this model remains unclear. Peripheral blood T lymphocytes were obtained from Balb/c mice fed a magnesium-deficient diet (approximately 1.8 mmol Mg/kg), or the same diet supplemented with 20 mmol MgO/kg. These cells were incubated in medium containing 10(-10) to 10(-5) M SP, after which the cells were examined for expression of SP receptors and the supernatants were collected and examined by immunochemical techniques for the presence of T lymphocyte associated cytokines. SP stimulation induced the secretion of interleukin (IL)-2, 4, 5, 10, 12, 13 and interferon-gamma (IFN-gamma). T lymphocytes from magnesium-deficient animals, when compared to magnesium-sufficient ones, secreted increased levels of these cytokines. The secretion of these cytokines was maximal at either 5 days (IL-4, IL-5) or 7 days (II-2, IL-10, and IFN-gamma) of magnesium deficiency. This increased sensitivity to SP appears to be related to an increased expression of SP receptors on the surface of T lymphocytes during the first week of magnesium deficiency. These data indicate that SP released early during magnesium deficiency exerts a regulatory role on T lymphocyte cytokine production, especially those cytokines regulating mast cell and immune responses leading to the onset of an immunopathological state.
 ...
PMID:Immunoregulation by neuropeptides in magnesium deficiency: ex vivo effect of enhanced substance P production on circulating T lymphocytes from magnesium-deficient mice. 881 89

A close anatomical relationship between nerves containing substance P and calcitonin gene-related peptide (CGRP) and mast cells containing serotonin has been demonstrated in the rat lacrimal gland. This study investigates the potential for peptidergic regulation of lacrimal mast cells by examining the actions of substance P, CGRP and serotonin on protein and peroxidase secretion from isolated lacrimal segments and on substance P and CGRP to release serotonin from the lacrimal mast cells. Substance P, CGRP and serotonin evoked marked increases in total protein and peroxidase from the lacrimal. Sodium cromoglycate, a mast cell stabilizer, significantly reduced or blocked the secretory responses elicited by these agonists. Chromatographic analysis using electrochemical detection revealed that substance P, but not CGRP, augmented the release of serotonin from the gland. The substance P evoked peroxidase secretion and serotonin release was blocked by CGRP and by sodium cromoglycate. These results support a role for mast cells in the regulation of lacrimal secretion and suggest a novel regulatory interaction between substance P and CGRP in the control of lacrimal function through a neuro-immune interaction.
 ...
PMID:Secretion and serotonin release in the isolated rat lacrimal gland: the effects of substance P and calcitonin gene-related peptide. 891 52

To study the elements of neurogenic inflammation in psoriatic skin, morphological contacts were examined between mast cells and sensory nerves containing the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP). Because mast cells in psoriatic lesions appear in great numbers at the basement membrane (BM) zone, neuropeptide-mast cell contacts with the BM were also counted. A double stain for active mast cell tryptase and the neuropeptides was applied and the contacts were quantitated morphometrically. Sensory nerve-mast cell contacts were also studied three-dimensionally with a confocal laser scanning microscope. Increases in the contact values of SP and CGRP with mast cells, as well as with the BM, were obtained in developing (1-3 weeks) lesions when compared with their non-lesional controls. This increase reached statistical significance in mature lesions. In contrast, the corresponding contact values for VIP were decreased. By confocal microscopy, a close association between mast cells and sensory nerves was observed in the lesional dermis. Since tryptase is known to degrade CGRP but not SP, neurogenic stimuli, mainly via SP, can result in degranulation of mast cells, which release substances to enhance inflammation. At the BM zone in psoriatic lesions, the numerous mast cells loaded with tryptase can promote degradation of BM components and allow entry of various mediators to interact with keratinocytes.
 ...
PMID:Quantitative histochemical analysis of mast cells and sensory nerves in psoriatic skin. 897 81

The effect of topical application of clobetasol propionate ointment (0.05% w/v) on the vascular changes induced by intradermal injections of histamine, calcitonin gene-related peptide, substance P, endothelin-1 and compound 48/80 was studied. Clobetasol propionate ointment was applied topically under occlusion to the forearm skin of healthy volunteers and vehicle base was applied to the contralateral forearm. The intradermal injections were made 4 h or, in a separate study, 72 h after topical steroid application. Responses were measured by planimetry and laser Doppler flowmetry. Four hours application of steroid did not significantly alter the responses to any of the vasoactive substances. After 72 hours application, clobetasol propionate significantly increased the size of the endothelin-1-induced area of vasoconstriction (p < 0.02) and significantly reduced the size of the flares induced by endothelin-1 (p < 0.02), substance P (p < 0.009) and compound 48/80 (p < 0.05). We conclude that the most likely explanation of our data is an inhibition by the steroid of cutaneous mast cell function.
 ...
PMID:The effect of topical steroid on the actions of vasoconstrictor and vasodilator peptides in human skin. 899 May 3

We recently demonstrated that cultured malignant schwannoma (MS)-derived cells can support human skin mast cell (HSMC) survival in vitro. Cultured HSMCs were spindleshaped in close contract with MS-derived cells, suggesting cell to cell interaction. To elucidate the mechanism of the enhanced HSMC survival in coculture with MS-derived cells and the cellular interactions between HSMC and MS-derived cells, we examined the immunocytochemical characteristics of MS-derived cells using immunofluorescence. Morphologically, cultured MS-derived cells were polygonal with abundant cytoplasm and resembled perineurial cells. The cultured cells immunoreacted positively with vimentin, fibronectin, laminin and collagen IV, but negatively with anti-S100 protein, anti-neuron specific enolase, and anti-neurofilament (68 kd, 145 kd, 200 kd) antibodies. MS-derived cells were distinct from Schwann cells in their lack of S100 protein and also distinguishable from endoneurial fibroblasts that produce fibronectin, but never expressed laminin or collagen IV. MS-derived cells thus possess the characteristics of perineurial cells in their general morphology and their immunocytochemical properties. Immunoreactivity for substance P (SP) and neurokinin A (NKA) was found in the cytoplasm of these cells, particularly around the nuclei. Vasoactive intestinal peptide, somatostatin, and calcitonin gene related peptide were negative. From these findings, we characterized the MS-derived cell's in vitro properties and concluded that it is similar to a perineurial cell. The extracellular matrix protein, laminin, and fibronectin expressed in the MS-derived cell might contribute to HSMC survival and morphology through cell to matrix adhesion. Neuropeptides such as SP and NKA, expressed in the MS-derived cell, might play some role in enhanced HSMC survival in vitro.
 ...
PMID:Immunocytochemical characterization of malignant schwannoma-derived cells in culture. 904 33

In this study, we have characterized the phenotype of mast cells in rat dura mater and their topological and functional relationships with C-fibers in normal and inflammatory conditions. Three mast cell populations with different size, morphology and localization were characterized by their content of specific neutral serine proteases. They showed immunoreactivity corresponding to rat mast cell protease I, rat mast cell protease II, or both proteases. Using confocal microscopy, all three mast cell types were observed in close apposition (distance less than 100 nm) to calcitonin gene-related peptide- and substance P-immunoreactive nerve fibers in both controls and rats infected with the nematode Nippostrongylus brasiliensis. After nematode infection or neonatal treatment with capsaicin, a large increase in the number of rat mast cell protease II-immunoreactive mast cells was found within dura mater segments (+1478% and +596%, respectively), without concomitant changes of rat mast cell protease I- or rat mast cell protease I/II-immunoreactive mast cells. Under both these conditions, the increase in mast cell number was accompanied by a significant increase in rat mast cell protease II level within tissue extracts (+281% after nematode infection and +36% after capsaicin treatment). The functional interaction of mast cells with sensory nerve fibers in the dura mater was assessed by evaluating [3H]histamine synthesis after administration of L-[3H]histidine, an index of mast cell activity. The H3 receptor agonist (R)-alpha-methylhistamine (15 mg/kg, i.p.) had no effect, but administration of the H3 receptor antagonist, thioperamide (10 mg/kg, i.p.), resulted in a significant increase of [3H]histamine synthesis (+62%). This effect was reduced in neonatal capsaicin-treated rats, but not completely suppressed (+35%), very likely because of partial denervation, as assessed by monitoring calcitonin gene-related peptide immunoreactivity. It is concluded that, in the dura mater, as in peripheral tissues, sensory nerve fibers and mast cells actively synthesizing and releasing histamine form a short inhibitory feedback loop involving prejunctional H3 receptors that could regulate the release of pro-inflammatory mediators, thus limiting the extent of inflammatory reactions.
 ...
PMID:Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions. 907 Jul 55


<< Previous 1 2 3 4 5 6 7 8 9 Next >>