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)

To clarify the base of in vivo biological activities of peptidoglycans of Gram-positive bacteria, the effects of a polysaccharide peptide of Staphylococcus epidermidis peptidoglycan (SEPS) on the synthesis of histamine and putrescine in BALB/c mice were examined and compared with those of a lipopolysaccharide (LPS or endotoxin) of Gram-negative bacteria. Within a few hours after its injection into BALB/c mice, SEPS induced histidine decarboxylase (HDC), the enzyme forming histamine, in the liver, lung, spleen and bone marrow, and ornithine decarboxylase (ODC), the enzyme forming putrescine, in the tissues except for the lung. SEPS induced HDC activity even in mast cell-deficient mice and in nude mice. These effects of SEPS were essentially the same as those of LPS. However, the dosage of SEPS capable of inducing HDC and ODC was much higher (100 to 1,000 times) than that of LPS. We have reported that C3H/HeN mice are resistant to SEPS in producing acute arthritis, and their productions of IL-1 and prostaglandin E2 are less than BALB/c mice sensitive to producing acute arthritis. In the present study, it was also found that C3H/HeN mice were markedly resistant to SEPS in inducing HDC activity.
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PMID:Stimulation of the synthesis of histamine and putrescine in mice by a peptidoglycan of gram-positive bacteria. 807 26

The supernatant (CM) of long-term bone marrow culture (LTBMC) contains colony promoting activity (CPA) which does not have granulocyte-macrophage (GM) colony-stimulating activity but which enhances GM-colony formation in the presence of CSF. CPA is different from IL-1, IL-3 and GM, G-, and M-CSF. Since CPA-containing LTBMC-CM always contains a substantial level of IL-6, CPA was thought to be similar to IL-6. In the present study, we found that LTBMC with a particular batch of horse serum produced IL-6 without a corresponding production of CPA. Addition of IL-6 to GM-colony assay system in the presence of GM-CSF did not enhance the colony formation. LTBMC-CM did not stimulate proliferation nor differentiation of mast cell progenitors. Anti-IL-6 antibodies suppressed IL-6 activity, but not CPA. These results indicate that CPA is a novel factor distinct from IL-1, IL-3, G-, M-, GM-CSF, IL-6 and SCF (c-kit ligand).
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PMID:Colony promoting activity (CPA) is a novel factor distinct from IL-6. 821 51

The growth-promoting activities of interleukin-10 (IL-10) were assessed in hematopoietic colony-forming assays. We found that IL-10 failed to support the clonal growth of normal and lineage-depleted (Lin-) bone marrow (BM) cells. Furthermore, IL-10 neither enhanced nor suppressed colony formation by eosinophil, neutrophil, or macrophage progenitors when combined with a variety of factors. IL-10 stimulated a modest increase in erythropoietin (Epo)-dependent erythroid colonies but had no effect on the burst-promoting activities of IL-3. However, the combination of IL-10 plus IL-3 resulted in the enhanced growth of mast cell progenitors. In addition to its mast cell stimulating activity, IL-10 promoted the growth of megakaryocyte (Mk) and Mk-mixed colonies when combined with Epo or with Epo plus IL-3, IL-6, or IL-11. Comparative studies showed that the megakaryocyte potentiating activity of IL-10 is roughly equivalent to that of IL-6 and IL-11. In experiments using Thy1loSca1+ stem cells, IL-10 was shown to enhance the number of cells initiating IL-3-dependent colony formation. IL-10 also costimulated increased colony formation when used with IL-3 and another factor such as IL-1, IL-6, and granulocyte colony-stimulating factor (G-CSF). Cellular analysis of the resulting colonies indicated that IL-10 increases the formation of multilineage colonies containing erythrocytes, megakaryocytes, and/or mast cells. The ability of IL-10 to cooperatively regulate various stages of hematopoietic development is discussed.
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PMID:Interleukin-10 promotes the growth of megakaryocyte, mast cell, and multilineage colonies: analysis with committed progenitors and Thy1loSca1+ stem cells. 829 35

Release of inflammatory mediators by mast cells can be modulated by certain cytokines and by nitric oxide. An in vitro platelet aggregation bioassay was used to assess the effects of interleukin-1 beta (IL-1 beta) on the release of platelet-activating factor and nitric oxide from resting or ionophore-activated peritoneal mast cells (PMC) from rat. PMC spontaneously released a substance that inhibits thrombin-stimulated platelet aggregation. The activity of this substance is abolished by addition of hemoglobin to the platelet suspension and augmented by preincubation of the PMC with L-arginine, suggesting that it is nitric oxide. Within minutes, IL-1 beta concentration-dependently (1 pg/ml-100 ng/ml) enhanced the release from activated PMC of nitric oxide, as measured by its ability to inhibit thrombin-induced platelet aggregation, and as confirmed with a biochemical assay for nitrite. This action of IL-1 beta was inhibited by pretreatment of PMC with a calmodulin antagonist (calmidazolium), an IL-1 receptor antagonist, or either of two nitric oxide synthase inhibitors (L-NAME and LY-83583). IL-1 beta also inhibited the release of platelet-activating factor from PMC through a nitric-oxide-dependent mechanism. These results demonstrate that IL-1 beta is a potent and rapid-acting modulator of mast cell reactivity, stimulating nitric oxide release while inhibiting the production of platelet-activating factor.
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PMID:Modulation of rat mast cell reactivity by IL-1 beta. Divergent effects on nitric oxide and platelet-activating factor release. 839 60

We report that embryonic stem cells efficiently undergo differentiation in vitro to mesoderm and hematopoietic cells and that this in vitro system recapitulates days 6.5 to 7.5 of mouse hematopoietic development. Embryonic stem cells differentiated as embryoid bodies (EBs) develop erythroid precursors by day 4 of differentiation, and by day 6, more than 85% of EBs contain such cells. A comparative reverse transcriptase-mediated polymerase chain reaction profile of marker genes for primitive endoderm (collagen alpha IV) and mesoderm (Brachyury) indicates that both cell types are present in the developing EBs as well in normal embryos prior to the onset of hematopoiesis. GATA-1, GATA-3, and vav are expressed in both the EBs and embryos just prior to and/or during the early onset of hematopoiesis, indicating that they could play a role in the early stages of hematopoietic development both in vivo and in vitro. The initial stages of hematopoietic development within the EBs occur in the absence of added growth factors and are not significantly influenced by the addition of a broad spectrum of factors, including interleukin-3 (IL-3), IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. At days 10 and 14 of differentiation, EB hematopoiesis is significantly enhanced by the addition of both Kit ligand and IL-11 to the cultures. Kinetic analysis indicates that hematopoietic precursors develop within the EBs in an ordered pattern. Precursors of the primitive erythroid lineage appear first, approximately 24 h before precursors of the macrophage and definitive erythroid lineages. Bipotential neutrophil/macrophage and multilineage precursors appear next, and precursors of the mast cell lineage develop last. The kinetics of precursor development, as well as the growth factor responsiveness of these early cells, is similar to that found in the yolk sac and early fetal liver, indicating that the onset of hematopoiesis within the EBs parallels that found in the embryo.
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PMID:Hematopoietic commitment during embryonic stem cell differentiation in culture. 841 45

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.
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PMID:The role of stem cell factor (c-kit ligand) and inflammatory cytokines in pulmonary mast cell activation. 863 Mar 86

Pathologic fibroblast proliferation or tissue fibrosis develops in certain chronic allergic diseases and in a wide array of other inflammatory disorders in which mast cell activation is also a prominent feature. In this study we investigated a number of potential mechanisms by which IgE-dependent activation of mouse mast cells might influence the proliferation of mouse fibroblasts in vitro. We found that supernatants from in vitro-derived mast cells that had been activated by IgE and specific antigen (but not those from quiescent mast cells) promoted the proliferation of mouse embryonic skin or 3T3 fibroblasts, and we showed that this effect was detectable in the absence of fetal calf serum. We analyzed the kinetics with which the fibroblast-proliferative activity was secreted from bone marrow-derived cultured mast cells and found that it was released both rapidly (i.e., in 30 minutes or less) and for a more prolonged period (i.e., for more than 2 hours) after IgE-dependent mast cell activation. We then measured the levels at which the mast cells produce a number of cytokines that are known to affect fibroblasts (IL-1, IL-6, transforming growth factor-beta 1 [TGF-beta 1], and tumor necrosis factor-alpha [TNF-alpha]) and assessed their relative effects, as recombinant cytokines, on fibroblast proliferation. Our mast cells secreted high levels of TGF-beta 1 and TNF-alpha, intermediate amounts of IL-6, and low levels of IL-1. We titrated the fibroproliferative effects of each of these cytokines and determined that at a dose of 50 pg/ml their rank order of activity was TGF-beta 1 > TNF-alpha > IL-1 > IL-6, with all but IL-6 having significant effects. The ability of supernatants from activated bone marrow-derived cultured mast cells to promote fibroblast proliferation was partially diminished by absorption with neutralizing antibodies against either TNF-alpha or TGF-beta 1, and absorption of the supernatants with a combination of antibodies against TNF-alpha and TGF-beta 1 reduced their ability to induce fibroblast proliferation by approximately 50% (p < or = 0.001, n = 5). These findings show that IgE-dependent activation of mouse mast cells can result in the release of mediators that promote fibroblast proliferation in the absence of any other cell type and suggest that mast cell-derived TNF-alpha and TGF-beta 1 contribute substantially to this effect. They also suggest that these cytokines exert their effects through synergistic interactions with other mast cell mediators.
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PMID:Promotion of mouse fibroblast proliferation by IgE-dependent activation of mouse mast cells: role for mast cell tumor necrosis factor-alpha and transforming growth factor-beta 1. 900 19

The photochemotherapeutic value of topical 8-methoxypsoralen (8-MOP) plus UVA irradiation has been well recognized. The phototoxicity associated with psoralen plus UVA (PUVA) therapy is hallmarked by an increase in vascular permeability (iVP), the accumulation of polymorphonuclear leukocytes (aPMN) and erythema formation in situ. Rose bengal (RB) plus UVA-VIS light (320-700 nm) produces a similar acute inflammatory response, but without immediate or delayed erythema and perceptible edema. This study describes some of the parameters involved in inflammatory reactions evoked by PUVA and the results are compared with RB-induced phototoxic reactions. The rates of iVP and aPMN with a 3 h pulse were quantified using 125I-albumin and 51Cr-labelled PMNs respectively. The erythemal response was graded visually. 8-MOP cream was applied topically, while RB was injected intradermally in rabbit skin before UVA-VIS (9.4 J cm-2) irradiation. The data show that there is no significant difference in the rates of iVP, aPMN and erythema formation between normal skin sites and mast cell-depleted skin sites when challenged with 8-MOP plus light. These results suggest that in situ mast cells do not play a significant role in 8-MOP-photoinduced acute cutaneous inflammatory reactions, in contrast with RB-photoinduced reactions. The iVP and aPMN responses are minimal or absent in sites subjected to repeated exposure to 8-MOP plus light for three or more consecutive days, suggesting the establishment of a desensitized/unresponsive state. Moreover, 8-MOP-photo-desensitized sites do not produce iVP and aPMN of the same magnitude as the normal (naive) skin sites when challenged with RB plus light. Similarly, RB-photo-desensitized sites do not produce iVP and aPMN of the same magnitude as the native skin sites when challenged with 8-MOP plus light. The desensitization and cross-desensitization of skin sites to 8-MOP- or RB-photoinduced reactions suggest that there is either direct attack on the target cell(s), thereby removing the ability to express adhesion molecules, such as endothelial leukocyte adhesion molecule 1 (ELAM-1) or intercellular adhesion molecule 1 (ICAM-1), involved in the accumulation of inflammatory cells, or downregulation of the secretion/release of putative agent(s), such as interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), responsible for the initiation and progression of cutaneous inflammations.
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PMID:Comparative studies on the tolerance to photoinduced cutaneous inflammatory reactions by psoralen and rose bengal. 908 68

Interleukin 10 (IL-10) is a recently described natural endogenous immunosuppressive cytokine that has been identified in human, murine, and other organisms. Human IL-10 (hIL-10) has high homology with murine IL-10 (mIL-10) as well as with an Epstein-Barr virus genome product BCRFI. This viral IL-10 (vIL-10) shares a number of activities with hIL-10. IL-10 significantly affects chemokine biology, because human IL-10 inhibits chemokine production and is a specific chemotactic factor for CD8+ T cells. It suppresses the ability of CD4+ T cells, but not CD8+ T cells, to migrate in response to IL-8. A nonapeptide (IT9302) with complete homology to a sequence of hIL-10 located in the C-terminal portion (residues 152-160) of the cytokine was found to possess activities that mimic some of those of hIL-10. These are: (i) inhibition of IL-1beta-induced IL-8 production by peripheral blood mononuclear cell, (ii) inhibition of spontaneous IL-8 production by cultured human monocytes, (iii) induction of IL-1 receptor antagonistic protein production by human monocytes, (iv) induction of chemotactic migration of CD8+ human T lymphocytes in vitro, (v) desensitization of human CD8+ T cells resulting in an unresponsiveness toward rhIL-10-induced chemotaxis, (vi) suppression of the chemotactic response of CD4+ T human lymphocytes toward IL-8, (vii) induction of IL-4 production by cultured normal human CD4+ T cells, (viii) down-regulation of tumor necrosis factor-alpha production by CD8+ T cells, and (ix) inhibition of class II major histocompatibility complex antigen expression on IFN-gamma-stimulated human monocytes. Another nonapeptide (IT9403) close to the NH2-terminal part of hIL-10 did not reveal cytokine synthesis inhibitory properties, but proved to be a regulator of mast cell proliferation. In conclusion, we have identified two functional domains of IL-10 exerting different IL-10 like activities, an observation that suggests that relatively small segments of these signal proteins are responsible for particular biological functions.
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PMID:Identification of functional domains on human interleukin 10. 940 62

1. In vivo rectal distension (RD) induces a neurally mediated colonic net water hypersecretion in rats. Interleukin-1 beta (IL-1 beta) also induces neural colonic water hypersecretion involving the release of prostaglandins (PGs) and a mast cell degranulation in rats. This study investigated in vivo the role of IL-1, PGs and mast cells in RD-induced colonic hypersecretion. 2. Proximal colonic net water flux was determined using [14C]polyethylene glycol (PEG) 4000 (mol. wt. 4000) in anaesthetized rats. On strips taken from the distal colon: (i) a histological analysis was performed to determine the number of mucosal mast cells (MMC); and (ii) histamine levels were measured by radioimmunoassay after stimulation with compound 48/80. 3. RD induced a net colonic water secretion that was blocked by i.c.v. administration of IL-1ra (an IL-1 receptor antagonist) and indomethacin, and by systemic treatment with doxantrazole and indomethacin. RD decreased the number of resident mast cells and the release of histamine from the distal colonic strips. Moreover, using SDS-PAGE immunoblotting the expression of IL-1 beta was detected in the brain. 4. These results suggest that, in rats, RD induces colonic net water hypersecretion by the activation of a neuro-immunological reflex pathway, involving IL-1 beta, PG release and peripheral mast cell degranulation.
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PMID:Involvement of interleukin-1, prostaglandins and mast cells in rectal distension-induced colonic water secretion in rats. 948 85


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