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)

Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminary in vitro experiments indicated that doxorubicin (10(-6) to 2.5 X 10(-4) M), in contrast to compound 48/80 and the calcium ionophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. In in vitro experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10(-5) to 3.3 X 10(-3) M revealed that all caused histamine release, with 10(-3) M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5 X 10(-6) M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent. The results indicate that in vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat sin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparations in vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.
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PMID:Anthracycline-induced histamine release from rat mast cells. 618 75

The influences of season and anaesthetic on the cutaneous vascular permeability responses to histamine (2.5 X 10(-8) mol), serotonin (5HT, 2.5 X 10(-10) mol), and to the mast cell-releasing agents adenosine 5(1)-triphosphate (2.5 X 10(-7) mol), dextran (5 X 10(-5) g) and compound 48/80 (1 X 10(-7) g) were examined using an Evans blue dye leakage technique. In rats anaesthetized with urethane (1 g/kg i.p.), responses to irritants were significantly less than in rats given ether for the period of administration of irritants and allowed to recover consciousness. The response to histamine was mediated by H1-receptors since it was abolished by mepyramine but not by metiamide. The only seasonal variation observed was in responses to 5HT in urethane-anaesthetized rats, which were significantly less in winter than in summer. It was concluded that dye leakage responses to irritants are affected more by anaesthetic than by seasonal variation.
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PMID:Influence of season and anaesthetic on cutaneous vascular permeability responses to histamine, serotonin and mast cell-releasing agents in rats. 619 25

The potent vasoactive and leukotactic properties of acetyl glyceryl ether phosphorylcholine (AGEPC) were further characterized histologically. After intravenous infusion of colloidal carbon and local injection of AGEPC, microscopic examination of rat cremaster muscle and skin revealed histamine-like vascular labeling restricted to postcapillary venules. Ultrastructural studies demonstrated subendothelial carbon accumulation in labeled venules. In rat skin, vascular labeling with colloidal carbon was an equally sensitive indicator of AGEPC-induced vasoactivity as was Evans blue dye extravasation for the assessment of AGEPC-induced increased vascular permeability (i.e., 1 pmole of AGEPC consistently initiated both vascular labeling and increased vascular permeability). In addition to its potent vasoactive effects in rabbits and rats, concomitant leukocyte emigration was observed in venules within 15 minutes after intradermal injection of AGEPC. In rabbit skin, AGEPC was equally as potent for the induction of leukocyte infiltrates as for the stimulation of increased vascular permeability. However, the vasoactive properties of AGEPC appeared to be neutrophil independent as well as independent of mast cell and platelet stimulation; these data suggest that AGEPC may act upon the microvasculature by direct stimulation of the venular endothelial cells. Thus, the putative role of AGEPC as a potent inflammatory mediator includes both the vasoactive and the leukotactic aspects of the acute inflammatory process.
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PMID:Morphologic basis of increased vascular permeability induced by acetyl glyceryl ether phosphorylcholine. 669 49

The pharmacology of the early and delayed phases of the neurogenic oedema responses to electrical stimulation of the saphenous nerve was studied in anesthetized rats using a quantitative Evans blue dye leakage technique. The immediate response to 5 min nerve stimulation was not reduced by aprotinin or mepyramine in combination with methysergide. However the response measured 10 min later and also that to 15 min nerve stimulation were reduced by these agents indicating that kinins and mast cell amines might be released after some delay, but they did not contribute significantly to the early phase of the response. Results with indomethacin indicated that prostaglandins were not involved in the later phase of the response. Bacitracin which has been reported to potentiate the sialogogic effect of substance P, the most likely candidate for primary mediator of neurogenic oedema, was without effect on the early phase of the response. Morphine, which has been suggested to inhibit stimulus-evoked substance P release from primary afferent terminals, reduced the early phase of the neurogenic oedema response but it also reduced blood pressure. Both effects were abolished by naloxone and thus it is likely that the reduction in the neurogenic oedema response was due to the depressor action of morphine. In confirmation of previous findings, capsaicin pretreatment of both adult rats and rats as neonates resulted in marked reduction of the neurogenic oedema response without effect on the vascular permeability response to substance P.
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PMID:Pharmacology of the neurogenic oedema response to electrical stimulation of the saphenous nerve in the rat. 723 72

The soluble granule chymase, rat mast cell protease-II (RMCP-II), is abundantly expressed in intestinal mucosal mast cells (MMC) but its function is not known. One hypothesis is that RMCP-II degrades the epithelial basement membrane and promotes the loss of enterocytes typically associated with type I hypersensitivity reactions in the rat. To test this hypothesis more directly, ex vivo perfusion of the cranial mesenteric artery and jejunal lumen was used to monitor the anaphylactic release of RMCP-II and its effects on mucosal permeability and epithelial integrity. Within 2 min of intravascular challenge with soluble adult Nippostrongylus brasiliensis worm antigen there was a 1,000-fold (P < 0.02) increase in the concentration of RMCP-II in the vascular perfusate from the jejunum of Nippostrongylus-sensitized rats but not the controls. Similarly, translocation of RMCP-II into the gut lumen increased 10-fold (P < 0.02) after 2 min only in worm antigen-challenged immune rats. Using an identical protocol, but incorporating Evans blue-labeled human serum albumin (EB-HSA) in the vascular perfusate, the timing of the release of RMCP-II into the two compartments was very similar to the first experiment and furthermore the translocation of EB-HSA increased 18-fold (P < 0.05) after 4 min in sensitized rats challenged with worm antigen. To examine the effects of RMCP-II more directly 1 mg of the highly purified chymase was introduced into the cranial mesenteric artery in ex vivo perfused normal rats. A significant (P < 0.05) 70-fold increase in concentration of RMCP-II in jejunal perfusate occurred after 6 min. In a repeat dose-response experiment, infusion of 0.375, 0.75, or 1.5 mg of RMCP-II, together with EB-HSA, established that the cumulative amounts of RMCP-II and EB-HSA translocated from the vasculature to the gut lumen in each perfusion (during the 10-min period of RMCP-II infusion) were significantly correlated. Analysis of intestinal perfusates by SDS-PAGE and by Western blotting using monoclonal anti-RMCP-II antibody confirmed that there was a concomitant translocation of both the protease and EB-HSA into the gut lumen. Histological evaluation of the mucosa failed to reveal any significant morphological change in any of the experiments. The rapid development of macromolecular leak, its association with the translocation of RMCP-II, and the absence of gross epithelial lesions, suggest for the first time that a mast cell granule chymase increases epithelial permeability via a paracellular route and implies that the substrate may be a protein, or proteins, in the epithelial junctional complex.
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PMID:Release of the mucosal mast cell granule chymase, rat mast cell protease-II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum. 750 33

Human recombinant interleukin-1 receptor antagonist (rhIL-1ra), a 17.2 kd protein is currently in clinical trials for the treatment of rheumatoid arthritis (RA). Skin reactions in some patients with RA prompted investigation of a possible pathogenesis involving nonimmunologically mediated mast cell degranulation. Rats injected intradermally with 20 microliters of rhIL-1ra (100 or 200 mg/ml) or the rhIL-1ra vehicle CSEP (10 mmol/L Na-citrate, 0.5 mmol/L ethylenediaminetetraacetic acid (EDTA), 0.1% polysorbate 80, 140 mmol/L NaCl, pH 6.5) had marked (15x or 10x, respectively) Evans blue dye permeability increases as compared with rats injected with phosphate-buffered saline solution (PBS) or bovine serum albumin (BSA). The permeability changes were reduced or eliminated by subcutaneous or local treatment with the antihistamine diphenhydramine. Histologic evaluation of skin sections from rats injected intradermally with CSEP or rhIL-1ra in CSEP revealed mast cell degranulation and edema, features not seen in sites injected with PBS or BSA in PBS. Components of the vehicle were investigated individually for their capacity to cause the reaction. Na-citrate (10 mmol/L) induced a greater increase in permeability than did EDTA (0.5 mmol/L) or polysorbate 80 (0.1%), and all produced reactions that were significantly greater than those occurring at PBS-injected sites. Evans blue dye permeability increases after subcutaneous injection of 1 ml of rhIL-1ra (100 mg/ml) in CSEP (with and without diphenhydramine) or rhIL-1ra in PBS were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cutaneous mast cell degranulation in rats receiving injections of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and/or its vehicle: possible clinical implications. 770 5

A hapten (DNP) model of topically induced ocular anaphylaxis has been developed. Rats immunized with DNP-Ascaris were skin-tested with DNP-bovine serum albumin (DNP-BSA) and Evans blue and challenged topically with varying amounts of di-DNP-lysine. The degree of clinical conjunctival edema was assessed, and eye tissues were evaluated histologically. Clinical conjunctival edema and histologic mast cell degranulation increased with higher concentration of di-DNP-lysine. In general, rats with positive skin tests showed more clinical conjunctival edema and more mast cell degranulation than those with negative skin tests. Three other groups of rats with positive skin tests to the DNP-BSA were injected intravenously with 125I-BSA and challenged topically with di-DNP-lysine. Retention of 125I-BSA in ocular adnexa and in globes was higher in di-DNP-lysine- than in PBS-challenged eyes. The hapten model simulates the ocular component of human hay fever in that ocular anaphylaxis is induced in immunized rats by topical challenge with antigen alone.
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PMID:A hapten model of topically-induced ocular anaphylaxis in the rat. 859 6

We tested the hypothesis that mast cells contribute to platelet-activating factor (PAF)-induced airways hyperreactivity and hyperpermeability in mice. Airways reactivity to acetylcholine (ACh) and lung permeability to Evans blue (EB) dye were measured before and after PAF challenge in genetically mast cell-deficient (WBB6F1 W/Wv) and normal congenic (WBB6F1 +/+) mice, as well as mast cell-reconstituted (BMT W/Wv) mice. In addition, prostaglandin D2 (PGD2), a mast cell-specific mediator, was measured in the bronchoalveolar lavage (BAL) from +/+ and W/Wv mice to determine if lung mast cell activation was a consequence of PAF challenge. Genetically PAF-sensitive AKR/J mice were also treated with the mast cell stabilizer nedocromil prior to assessment of PAF effects on ACh reactivity. Intravenous PAF (10 micrograms/kg) induced a significant (P < 0.05) increase in airways reactivity to ACh (25 micrograms/kg) in both +/+ (371 +/- 52%) and W/Wv (122 +/- 24%) mice. There was a significantly greater increase in +/+ compared with W/Wv mice. PAF-induced hyperreactivity to ACh in BMT W/Wv mice (191 +/- 44%) was significantly (P < 0.05) greater than age-matched W/Wv mice (80 +/- 16%), but not significantly different from age-matched +/+ mice (153 +/- 44%). PAF (10 micrograms/kg) also significantly (P < 0.5) increased lung permeability in +/+ and W/Wv mice, but there was no significant difference between groups. BAL PGD2 increased significantly in +/+ mice following PAF challenge (559 +/- 24 ng/ml) compared with vehicle controls (152 +/- 8 pg/ml). There was no significant increase in BAL PGD2 from W/Wv mice. Nedocromil pretreatment significantly (P < 0.05) decreased PAF-induced hyperreactivity in AKR/J mice but not in W/Wv mice (P > 0.05). We conclude that mast cells contribute significantly to PAF-induced hyperreactivity but not hyperpermeability in mice.
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PMID:PAF-induced airways hyperreactivity is modulated by mast cells in mice. 862 51

A rat model of inflammation was used to investigate the biological effects of thrombin. The thrombin-specific inhibitor Hirulog markedly attentuated the carrageenin-induced edema of the paw of the rat. Injection of thrombin into the paw also produced edema. The effect of thrombin was due to activation of its receptor; a thrombin receptor activating peptide (TRAP) reproduced the effects of thrombin in causing edema. TRAP also increased vascular permeability as demonstrated by extravasation of Evans blue and 125I-labeled serum albumin. The release of bioactive amines played an important role in mediating the TRAP-induced edema; the serotonin/histamine antagonist cryproheptadine and the histamine H2 receptor antagonist cimetidine reduced significantly the edema caused by TRAP. Treatment of rats with the mast cell degranulator 48/80 to deplete these cells of their stores of histamine and serotonin abolished completely the ability of TRAP to produce edema. Histochemical examination confirmed that TRAP treatment led to mast cell degranulation. Thus, it has been possible to demonstrate that thrombin acts as an inflammatory mediator in vivo by activating its receptor, which in turn leads to release of vasoactive amines from mast cells.
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PMID:Thrombin functions as an inflammatory mediator through activation of its receptor. 864 86

To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (l-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 micrograms), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 micrograms/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 micrograms/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.
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PMID:Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways. 876 28


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