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)

The effects of mast cell granules (MCGs) on macrophage-mediated lysis of P815 mastocytoma cells and nitric oxide (NO) production were studied. Murine peritoneal macrophages exhibited tumor cell killing and NO production only when activated with lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma). Coincubation of macrophages with MCGs during LPS activation dose-dependently inhibited macrophage-mediated tumor cell lysis. The MCG effect was not due to inactivation or removal of LPS by MCG. The inhibitory effect was also not due to histamine or serotonin present in the MCGs. The granules were not toxic to macrophages or P815 mastocytoma cells. The effect of MCGs on macrophage-mediated tumor cell killing was evident whether MCGs were added before or after a 4-h exposure of macrophages to LPS. However, the inhibitory effect was not seen if MCGs were added after macrophages had been exposed to LPS for 24 h. To assess whether MCGs could inhibit a non-LPS trigger, MCGs were tested on macrophages activated with IFN-gamma. In these experiments, MCGs dose-dependently inhibited macrophage-mediated tumor cell killing induced by IFN-gamma, LPS, or IFN-gamma plus LPS. Furthermore, in parallel experiments, MCGs significantly inhibited macrophage NO production induced by LPS, IFN-gamma, or IFN-gamma plus LPS. Pretreatment of MCGs with diisopropylfluorophosphate, a serine protease inhibitor, only partially abrogated the effects of MCGs. The results demonstrate that MCGs inhibit both LPS- and IFN-gamma-induced macrophage killing of P815 cells and the inhibition is associated with the decrease of NO production.
 ...
PMID:Mast cell granules inhibit macrophage-mediated lysis of mastocytoma cells (P815) and nitric oxide production. 848 25

Mast cells play a critical role in allergic airway responses via IgE-specific activation and release of potent inflammatory mediators. In the present study, we have isolated and characterized primary mast cell lines derived from the upper airways of normal mice. The primary mast cell lines were grown and maintained by incubation with interleukin-3 (IL-3) and stem cell factor (SCF) and shown to be c-kit (SCF receptor) positive by flow cytometry. Subsequently, we examined the proliferation of both airway and bone marrow derived mast cell lines in response to inflammatory and hematopoietic cytokines, including SCF, IL-1, IL-3, interferon-gamma, IL-4, and IL-10. The results from the pulmonary mast cell lines were compared with those from bone marrow derived mast cells. Pulmonary mast cell lines were capable of proliferating in response to IL-3, IL-4, IL-10, and SCF, whereas the combination of SCF with the other cytokines did not increase the response over SCF alone. In contrast, the bone marrow-derived mast cells proliferated strongest to SCF or IL-3, but only modestly to IL-4 and IL-10. Furthermore, the combination of SCF with IL-3, but not the other cytokines, exhibited an increase in bone marrow-derived mast cell proliferation. Cytokine-specific stimulation of histamine release in the airway-derived and bone marrow-derived mast cells showed parallel results. SCF was the only cytokine shown to induce substantial histamine release. However, when certain nonhistamine releasing cytokines were combined with SCF, a synergistic increase in histamine release was induced in upper airway, but not bone marrow-derived mast cells. The results of these studies suggest that cytokines differentially modulate induction of proliferation and degranulation of bone marrow and upper airway-derived mast cells and may further indicate a cytokine activational cascade in tissue mast cells.
 ...
PMID:The role of stem cell factor (c-kit ligand) and inflammatory cytokines in pulmonary mast cell activation. 863 Mar 86

The expression of the receptor for the anaphylatoxin C5a (C5aR, CD88) on the human mast cell line HMC-1 was studied with four anti-C5aR monoclonal antibodies directed to the N-terminal domain of the receptor. All antibodies bound to the human mast cell line HMC-1. The binding could be blocked by recombinant C5a and by peptide EX-1 representing amino residues 1-31 on the N-terminal domain of the C5aR. In addition, FITC-labelled C5a bound to HMC-1, and this binding could be blocked by unlabelled C5a or C5aR antibodies. C5aR-specific mRNA was detected in HMC-1 cells by RT-PCR which confirmed the expression of the C5aR gene made by these cells. Lymphocyte-conditioned medium, interferon-gamma or phorbol esters which have been shown to induce a down-regulation of C5aR on myeloid cells did not influence the expression of C5aR on HMC-1. C5a led to a transient mobilization of intracellular calcium in HMC-1 which could be inhibited by pre incubation of C5a with a C5a-specific antibody. In contrast to findings with granulocytes, HMC-1 did not respond to C5a(desArg), confirming previous findings with human skin mast cells. The findings show that (i) although HMC-1 differ from granulocytes in their responsiveness to C5a(desArg), they express similar C5aR and (ii) HMC-1 cells resemble skin mast cells in the expression and function of C5aR and may therefore serve as a model in future studies addressing the biology of this anaphylatoxin receptor on skin mast cells.
 ...
PMID:The human mast cell line HMC-1 expresses C5a receptors and responds to C5a but not to C5a(desArg). 869 89

Mast cells are pleiotropic bone marrow-derived cells found in mucosal and connective tissues and in close apposition to neurons, where they play important roles in tissue inflammation and in neuroimmune interactions. Connective tissue mast cells, with which intracranial mast cells share many characteristics, contain cytokines that can cause inflammation. Here, we report that myelin basic protein, a major suspected immunogen in multiple sclerosis, as well as an antigenic stimulus, provokes mast cells to trigger a delayed cytotoxicity for neurons in mixed neuron-gila cultures from hippocampus. Neurotoxicity required a prolonged period (12 h) of mast cell incubation, and appeared to depend largely on elaboration of the free radical nitric oxide by astrocytes. Activation of astrocytes was mediated, in part, by mast cell-secreted tumor necrosis factor-alpha. Myelin basic protein and 17 beta-estradiol had a synergistic action on the induction of mast cell-associated neuronal injury. The cognate mast cell line RBL-2H3, when subjected to an antigenic stimulus, released tumor necrosis factor-alpha which, together with exogenous interleukin-1 beta (or interferon-gamma), induced astroglia to produce neurotoxic quantities of nitric oxide. A small but significant proportion of mast cell-derived neurotoxicity under the above conditions occurred independently of glial nitric oxide synthase induction. Further, palmitoylethanolamide, which has been reported to reduce mast cell activation by a local autacoid mechanism, decreased neuron loss resulting from mast cell stimulation in the mixed cultures but not that caused by direct cytokine induction of astrocytic nitric oxide synthase. These results support the notion that brain mast cells could participate in the pathophysiology of chronic neurodegenerative and inflammatory diseases of the nervous system, and suggest that down-modulation of mast cell activation in such conditions could be of therapeutic benefit.
 ...
PMID:Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway. 876 79

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

We previously showed that interleukin-3 (IL-3) alone is not sufficient, although it is essential for murine mucosal-type mast cell development and that prostaglandin E (PGE) and interferon-gamma (IFN-gamma) are critical for survival or differentiation of mast cell precursors. We also confirmed that IL-4 is a key inhibitor for mast cell precursors despite being a growth factor of mast cells. In the present work, mouse spleen cells were cultured with recombinant (r) IL-1 beta, rIL-5, rIL-6, rIL-9, granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), tumor transforming growth factor-beta (TGF-beta), or tumor necrosis factor-alpha (TNF-alpha) in the presence of endogenous IL-3. After 12 days of culture, mast cell development was induced by rIL-6 and rTNF-alpha, rIL-1 beta, rIL-5, rGM-CSF, rTGF-beta and even the mast cell growth factors, rIL-9 and rSCF, failed to induce mast cell development. However, unlike IL-9 and SCF, IL-6 and TNF-alpha did not promote the growth of mast cells already developed. Macrophage may be one of the responsive cells of IL-6 and TNF-alpha in the cultures, because removal of macrophages greatly reduced the mast cell development induced by the cytokines. The actions of TNF-alpha and IL-6 were inhibited by indomethacin, an inhibitor for prostaglandin synthesis, and by neutralizing anti-IFN-gamma and anti-IL-3 antibodies. rIL-4, when added at the start of the culture, also inhibited mast cell development induced by rIL-6 and rTNF-alpha. Nevertheless, neutralizing anti-IL-6 and anti-TNF-alpha antibodies did not suppress mast cell development induced by PGE and IFN-gamma. TNF-alpha and IL-6 enhanced IFN-gamma production, but suppressed IL-4 production in the cultures. Mast cell numbers induced were inversely and directly proportional to IL-4 and IFN-gamma levels, respectively. These results indicate that inflammatory mediators as triggers are important for mast cell development although they are not the mast cell growth factors.
 ...
PMID:Tumor necrosis factor-alpha- and interleukin-6-triggered mast cell development from mouse spleen cells. 900 55

In the first three weeks of primary Giardia muris infections B10 mice clear infection more rapidly than BALB/c mice. There is evidence that interferon-gamma contributes to the relative resistance of B10 mice. The nature of the functional contribution of interferon-gamma is unclear and does not relate to the secretory or serum antibody response. Mucosal inflammatory events in these strains have been studied. Apart from a small rise in both strains of goblet cell and mucosal mast cell numbers, associated with release of mast cell protease-1 in serum, no inflammatory infiltrate was observed at the time trophozoites were cleared from the intestinal lumen. Inhibition of mast cell products (5-hydroxytryptamine and histamine) by cyproheptadine enhanced the intensity of infection in both strains. The relative resistance of B10 mice could not be explained in terms of the mucosal inflammatory response.
 ...
PMID:A comparison of mucosal inflammatory responses to Giardia muris in resistant B10 and susceptible BALB/c mice. 910 19

Alcohol consumption has been shown to be associated with immune suppression and immune modulation. In this study, the effects of ethanol ingestion on the host immune responses to Trichinella spiralis infection and the subsequent secretion of T-helper cell-associated cytokines were investigated in rats. At the early phase of T. spiralis infection, ethanol-fed animals showed decreased numbers of blood neutrophils and eosinophils, and a decreased secretion of interferon-gamma (IFN-gamma) by mesenteric lymph node cells, compared with pair-fed controls. Suppression of this early inflammatory response to infection in the ethanol-treated groups resulted in a slower rate of expulsion of intestinal adult worms and a higher fecundity rate for female worms, compared with pair-fed controls. A dramatic decrease in blood neutrophils in the ethanol-treated groups was also manifested on day 9 postinfection. At that time, mesenteric lymph node cells from the ethanol-treated groups secreted higher amounts of mast cell proliferation-enhancing activity, which has been shown to contain T-helper type 2-associated cytokines. At the later phase of infection (day 12 to 20 day postinfection), ethanol-treated animals contained higher numbers of blood eosinophils and secreted an increased amount of interleukin-5 and mast cell proliferation-enhancing activity, compared with pair-fed controls. Although there was a slight rise with time after infection, the level of serum corticosterone was not significantly increased in the ethanol groups. Therefore, it is not likely that the observed immune modulations caused by ethanol consumption, especially in the early phase of infection, is the effect of elevated levels of corticosterone in the circulation. The present study found that ethanol consumption suppressed the initial amount of interferon-gamma secretion and inflammatory response, and may have directly or indirectly led to an enhancement of the secretion of T-helper type 2-type cytokines later in the primary immune response to T. spiralis infection.
 ...
PMID:Ethanol consumption suppresses cell-mediated inflammatory responses and increases T-helper type 2 cytokine secretion in Trichinella spiralis-infected rats. 934 76

This review examines our current understanding of the mechanisms underlying allergic diseases. The IgE molecule plays a central role in the pathogenesis of immediate hypersensitivity reactions by virtue of its capacity to bind specifically to high-affinity IgE receptors on mast cells and mediate the release of various mast cell-derived mediators and proinflammatory cytokines on exposure to allergen. Clinically significant allergic responses are followed by a late-phase response dominated by eosinophils and T lymphocytes. The majority of T cells in allergic responses are memory T cells secreting helper type 2 (TH2)-like cytokines, i.e., interleukin (IL)-4, IL-5, IL-13, but not interferon-gamma. These cytokines regulate IgE synthesis and promote eosinophil development, thus contributing to allergic inflammatory responses. Failure to control immune activation early in the course of allergic disease blunts responses to glucocorticoid therapy and contributes to disease progression. The identification of key cells and molecules involved in the initiation and maintenance of allergic inflammation is likely to become an important target in the treatment of this common group of illnesses.
 ...
PMID:Molecular basis of allergic diseases. 960 37

Since data on the ability of human mast cells to produce various cytokines are scanty, we examined the mRNA expression, its modulation and the resulting protein expression of a number of well-characterized cytokines, using semi-quantitative reverse transcription-polymerase chain reaction of cell extracts and enzyme-linked immunosorbent assays for analysis of cell supernatants. One million cells/ml of the human mast cell line HMC-1 were stimulated with 25 ng/ml phorbol myristate acetate (PMA), 5 x 10(-7) M calcium ionophore A 23187 (ionophore) or both stimuli combined for various time periods. Constitutive expression in unstimulated cells was found for interleukin-1 beta (IL-1 beta) -3, -4, -8, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Maximal mRNA up-regulation was observed by 2-4 hr, with a second peak for TNF-alpha at 24 hr. After a 4-hr stimulation, IL-13 expression was detectable as well, whereas for IL-12, only the p35 but not the p40 chain was found, and IL-2, -5, -7 and interferon-gamma (IFN-gamma) were not expressed at all. Large quantities of IL-8, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 were secreted time-dependently over a 72-hr period, with lower levels of IL-1 beta, -6, -10 and TGF-beta and no detectable IL-2, -4 and IFN-gamma protein. When IL-6 and IL-8 expression was compared in more detail, IL-6 mRNA was found to be up-regulated only with ionophore but not PMA, whereas both stimuli alone or combined increased IL-8 mRNA expression. Preincubation with cycloheximide inhibited IL-6 but not IL-8 transcription, and incubation of stimulated cells with actinomycin D stabilized IL-8 and also IL-6 mRNA. These data suggest a selective regulation of distinct cytokines in human mast cells at the transcriptional and post-transcriptional levels. Furthermore, the spectrum of cytokines produced by HMC-1 cells supports the well-recognized role of mast cells in immediate-type hypersensitivity reactions as well as their potential colony-stimulating and tissue-remodelling abilities.
 ...
PMID:Comparative cytokine gene expression: regulation and release by human mast cells. 961 81


<< Previous 1 2 3 4 5 6 Next >>