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Biomedical subjects

S Mue

Publications and source records attributed to S Mue.

At least 55 records · Page 3Linked to original sources
PubMed1992

Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats.

In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammatory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4 micrograms/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutrophil infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37 degrees C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact rats. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.

Animals↗
PubMed1992

Analysis of the leukotriene D4 receptor in the granulation tissue of allergic inflammation in rats.

Leukotriene (LT) D4 receptor in the granulation tissue formed in the air pouch-type allergic inflammation model in rats was analyzed. Membrane preparation of the granulation tissue obtained 3-9 days after the antigen challenge has specific binding sites of [3H]LTD4. Scatchard analysis showed that the affinity (Kd) and the density (Bmax) were not changed among the granulation tissue obtained 3-9 days after the antigen challenge. The Kd value in the granulation tissue (0.90 +/- 0.12 nM) was close to that in the rat lung (1.00 +/- 0.24 nM) and the guinea pig lung (0.86 nM). On the other hand, Bmax (62 +/- 8 fmol/mg protein) in the granulation tissue was higher than that in the rat lung (21 +/- 4 fmol/mg protein) but was far less than that in the guinea pig lung (405 fmol/mg protein). LTC4 and LTE4 inhibited the binding of [3H]LTD4 to the membrane preparation of the granulation tissue in a concentration-dependent manner. IC50 of LTC4 and LTE4 were 1 x 10(-7) and 2 x 10(-7) M, respectively. A guanine nucleotide, guanyl-5'-yl-imido-diphosphate (GppNHp), reduced [3H]LTD4 binding to the membrane preparation of the granulation tissue suggesting that LTD4 receptors in the granulation tissue are associated with G proteins. These results indicate that LTD4 binding sites in the granulation tissue are high affinity receptors for LTD4. A possible role of LTD4 in the recurrence of allergic inflammation in the chronic phase is discussed.

Animals↗
PubMed1991

Downward regulation of neutrophil infiltration by endogenous histamine without affecting vascular permeability responses in air-pouch-type carrageenin inflammation in rats.

The role of histamine in neutrophil infiltration and vascular permeability response in carrageenin air pouch inflammation in rats was examined. Injection of carrageenin solution into an air pouch induced a gradual increase in histamine content in the pouch fluid and histidine decarboxylase activity of pouch wall tissues, with a maximum attained at 24 h. Local administration of the H2 antagonists cimetidine and famotidine, but not the H1 antagonist pyrilamine, induced an increase in neutrophil infiltration at 24 h. Both types of histamine antagonists failed to suppress the vascular permeability response. In addition, H2 antagonists attenuated the inhibitory effect of indomethacin on neutrophil infiltration without affecting the indomethacin-induced suppression of vascular permeability response. These results suggest that histamine produced in the inflammatory locus exerts a downward regulation of neutrophil infiltration through H2 receptors but does not play any significant role in the vascular permeability response. Furthermore, the inhibition by indomethacin of neutrophil infiltration might be ascribed to the increase in histamine level in the pouch fluid.

Anaphylaxis↗
PubMed1991

Stimulation of neutrophil adherence to vascular endothelial cells by histamine and thrombin and its inhibition by PAF antagonists and dexamethasone.

1. In order to clarify the roles of platelet-activating factor (PAF) in histamine- and thrombin-induced neutrophil adhesion to vascular endothelial cells, the effects of several PAF antagonists were examined. The effects of the glucocorticoid dexamethasone were also examined in order to gain further insight into the anti-inflammatory actions of glucocorticoids. 2. In culture, histamine and thrombin stimulated the adherence of rat peritoneal neutrophils to human endothelial cells from the umbilical vein. They did not stimulate neutrophil adherence in the absence of endothelial cells, suggesting that the target cells for the histamine- and thrombin-induced adherence of neutrophils were endothelial cells, not neutrophils. 3. Several PAF antagonists, such as CV-3988, L-652,731 and Y-24,180 inhibited the histamine- and thrombin-induced neutrophil adherence in a concentration-dependent manner. Indomethacin failed to inhibit it. 4. Dexamethasone, a steroidal anti-inflammatory drug, did not inhibit the histamine- and thrombin-induced adherence of neutrophils to endothelial cells when the drug was present only during the 20 min incubation period for the adherence assay. When the endothelial cells were preincubated for 3 h with dexamethasone, the adherence of neutrophils to endothelial cells induced by histamine or thrombin was not inhibited. 5. When the neutrophils were preincubated for 3 h with dexamethasone, the histamine- and thrombin-induced adherence of neutrophils to endothelial cells was inhibited. 6. Our studies indicate that: (a) adherence of neutrophils to endothelial cells induced by histamine and thrombin is mediated by PAF production since PAF antagonists inhibited the adherence of neutrophils; and (b) neutrophils, not endothelial cells, are the target cells through which dexamethasone acts to inhibit adherence.

Animals↗
PubMed1991

A role of peripheral leukocytes in vascular permeability and edema formation in air pouch type allergic inflammation in rats.

Using an air pouch type allergic inflammation model in rats, a role of circulating leukocytes in allergic inflammation responses was investigated by comparing normal rats with peripheral leukocytopenia rats induced by cyclophosphamide treatment. In the leukocytopenia rats, vascular permeability, edema formation, leukocyte infiltration into the pouch fluid, neutrophil chemotactic activity in the pouch fluid occurred both at the early phase (4 h) and the late phase (8 h) after the antigen challenge were decreased. However, edema formation induced by intradermal injection of arachidonate metabolites, serotonin, or platelet activating factor was not suppressed at all in the leukocytopenia rats. A possible role of peripheral leukocytes in allergic and non-allergic inflammation is discussed.

Animals↗
PubMed1990

Inhibition by dexamethasone of histamine production in allergic inflammation in rats.

In an allergic inflammation model of air pouch type in rats, histamine level in the pouch fluid and histidine decarboxylase activity of pouch wall tissues in the postanaphylaxis phase were increased. Although treatment with dexamethasone failed to inhibit histamine release from mast cells in the anaphylaxis phase, histamine production in the postanaphylaxis phase was inhibited dose dependently. Histamine production-increasing activity in the pouch fluid collected 8 h after the Ag challenge, which was estimated by an activity to stimulate histamine production by bone marrow cells, was decreased by the administration of dexamethasone at the time of the Ag challenge. The addition of steroidal antiinflammatory drugs, dexamethasone, prednisolone, or hydrocortisone, into the incubation medium inhibited the pouch fluid-induced histamine production by bone marrow cells. Hydrocortisone mesylate antagonized the inhibitory effect of dexamethasone on histamine production by bone marrow cells. However, hydrocortisone mesylate failed to recover the decrease in histamine production-increasing activity of the pouch fluid collected from dexamethasone-treated rats. In addition, the dialyzed sample of pouch fluid obtained from dexamethasone-treated nonsensitized rats did not reduce the stimulated histamine production by the pouch fluid sample obtained from the sensitized rats. However, increase in histamine production of bone marrow cells stimulated by the pouch fluid was not inhibited by cyclosporin A that inhibited histamine production induced by Con A. This observation indicates that the pouch fluid has no effect to induce production of the histamine production-increasing factor by bone marrow cells. Consequently, it is suggested that dexamethasone inhibits not only the production of histamine production-increasing factor but also the response of histamine-producing cells to this factor.

Animals↗
PubMed1990

Possible role for platelet-activating factor in neutrophil infiltration in allergic inflammation in rats.

Allergic inflammation was induced by injecting an antigen solution into an air pouch made on the dorsum of immunized rats with the antigen azobenzene-arsonate-conjugated acetyl bovine serum albumin. In this model, leukocyte infiltration into the pouch fluid was prominent 4-8 h after the antigen challenge. Most of the infiltrated leukocytes were neutrophils. Administration of the platelet-activating factor (PAF) antagonists such as CV-3988 and L-652,731 into the air pouch 15 min before and at the time of the antigen challenge failed to suppress leukocyte infiltration at 8 h. However, when the PAF antagonist was injected into an air pouch 4 h after the antigen challenge, neutrophil infiltration at 8 h was suppressed in a dose-dependent manner. Combined treatment with the 5-lipoxygenase inhibitor AA861 and the PAF antagonist did not potentiate the effect of the PAF antagonist, suggesting that participation of leukotriene B4 in neutrophil infiltration in this model is negligible. Eosinophil infiltration was very weak at 8 h, and the PAF antagonist showed no significant effect. At 8 h, the PAF level in the serum of the immunized rats was significantly higher than that of the nonimmunized rats. Intravenous administration of the PAF antagonist 15 min before the antigen challenge suppressed leukocyte infiltration more effectively than local administration into the pouch. These results indicate that PAF plays a significant role in neutrophil infiltration in allergic inflammation.

Animals↗
PubMed1990

Chemotactic activity for neutrophils in allergic inflammation in rats.

The number of neutrophils, eosinophils, and mononuclear cells that had migrated into pouch fluid were measured after injecting an antigen (azobenzenearsonate-conjugated acetyl bovine serum albumin) solution into air pouches made on the dorsum of immunized rats. The number of neutrophils began to increase 4 hr after the antigen challenge, reaching a maximum at 16-24 hr. Increases in the number of eosinophils and mononuclear cells were quite poor. The pouch fluid supernatant fraction was fractionated to hydrophilic and lipophilic fractions with the aid of an octadecylsilyl silica cartridge, and the chemotactic activity in each fraction was measured by the modified Boyden chamber method. The chemotactic activity in the pouch fluid supernatant fraction was the highest at 2-4 hr and decreased with time after the antigen challenge. At 16 and 24 hr, chemotactic activity was decreased to a very low level although there was a large number of neutrophils in the pouch fluid. At 4 hr, the chemotactic activity in the lipophilic fraction was significantly higher than that in the hydrophilic fraction. However, at 8 hr, the chemotactic activity in the lipophilic fraction was changed to a significantly lower level than that in the hydrophilic fraction. The chemotactic activity in the lipophilic fraction had decreased to a very low level at 8 hr. Heat treatment of the pouch fluid supernatant fraction at 92 degrees C for 5 min both at 4 and 8 hr significantly increased the chemotactic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A production of Dermatophagoides farinae allergen-specific IgE and Ig(G + M) antibodies by cultured peripheral blood mononuclear cells of patients with extrinsic bronchial asthma.

Using a modified reverse hemolytic plaque assay, we measured in vitro production of Dermatophagoides farinae allergen-specific IgE and Ig(G + M) antibodies by peripheral blood mononuclear cells in 19 patients with extrinsic bronchial asthma. Circulating the allergen-specific IgE was estimated by means of the Phadebas radioallergosorbent test system. We found a significant difference in the production of the allergen-specific IgE antibody by the cells between asthmatic patients with positive and negative circulating the allergen-specific IgE.

Adolescent↗
PubMed1987

Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma.

The bronchodilating effect of magnesium sulfate (MgSO4) was studied in ten asthmatic patients with mild attacks. In five patients, 0.5 mmol/min of MgSO4 was administered intravenously for 20 minutes, and the time courses of respiratory resistance, forced vital capacity, and forced expiratory volume at 1 s were studied. In another five patients, MgSO4 dose-response curves were obtained. Soon after administration began, MgSO4 relieved bronchoconstriction in a dose-dependent manner. Maximum responses (mean +/- SE) of respiratory resistance, forced vital capacity, and forced expiratory volume were 71% +/- 3%, 117% +/- 5%, and 118% +/- 1% of initial values, respectively, and were similar to the effects of additional albuterol inhalation. The infusion of MgSO4 also improved dyspnea and piping rales in three other asthmatic patients with a severe attack. We conclude that intravenous infusion of MgSO4 produces a rapid and marked bronchodilation in both mild and severe asthma and may be a unique bronchodilating agent.

Adult↗
PubMed1987

Bronchoalveolar lavage and histologic characterization of late asthmatic response in guinea pigs.

To elucidate the mechanisms of late asthmatic response (LAR) observed in asthmatic subjects, we have developed an animal model of LAR using guinea pigs. Fifty guinea pigs were immunized with a mixture of Ascaris suum extract and aluminum hydroxide and then challenged with an inhalation of Ascaris suum extract without anesthesia. Twenty of the 50 guinea pigs showed a dual asthmatic response in which the LAR occurred 3 to 6 h after immediate asthmatic response (IAR). Histologic studies by rapid freezing with liquid nitrogen or bronchoalveolar lavage (BAL) were performed in 14 of these 20 guinea pigs with LAR and compared with those in 10 of 18 guinea pigs with only IAR, 10 control guinea pigs, and 10 nonimmunized but challenged guinea pigs. Both the percentage and the absolute number of neutrophils in the BAL fluid of the guinea pigs with LAR were significantly greater than those of the control guinea pigs (p less than 0.02) and than those of the nonimmunized but challenged guinea pigs (p less than 0.02). However, that of guinea pigs with LAR was not significantly different from that of guinea pigs with only IAR. On the other hand, histologic examination showed that eosinophil infiltration within the airway walls of the guinea pigs with LAR was more prominent than that of the guinea pigs with only IAR, and showed that there was no significant difference in neutrophil infiltration within the airway walls between the guinea pigs with LAR and the animals with only IAR. Contraction of airway (bronchus, bronchiole) smooth muscle, submucosal edema, and mucus in airway lumen were also observed in LAR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Protective effects of ketotifen on allergen-induced bronchoconstriction and skin weal.

A single-blind cross-over method was used to investigate the effects of ketotifen on the total respiratory resistance response curve to inhalation of a high concentration of allergen (1:5 w/v house dust or 1:10 w/v Japanese cedar pollen) and the weal response to intradermal injection of serially diluted allergen (1:10(3)-1:10(6) w/v). Five subjects received 2 mg of ketotifen every 12 hr for the first week and an inactive placebo in the same manner for the second week. The remaining five subjects received the placebo for the first week and ketotifen for the second week. Ketotifen did not alter base-line pulmonary function, but significantly delayed the time from the start of allergen exposure to the beginning of elevation of total respiratory resistance (P less than 0.02), and the time from the start of allergen exposure to the point at which total respiratory conductance decreased by 35% from the base-line value (P less than 0.01). Ketotifen also decreased skin test sensitivity significantly (P less than 0.01).

Adult↗
PubMed1986

Bronchodilating effect of KC-404, a novel anti-asthmatic agent, and its derivatives in monkey.

The inhibitory effect of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine (KC-404) on aerosolized methacholine- and histamine-induced increase in total respiratory resistance (Rrs) was determined in monkeys using the forced 3 Hz oscillation method and was compared with the effect of aminophylline. The effects of several derivatives of KC-404 on methacholine-induced bronchoconstriction were also determined. All of the i.v. administered pyrazolopyridine derivatives showed an inhibition of the increase in Rrs induced by aerosolized methacholine. Among these derivatives, KC-404 exerted the most potent bronchodilating effect. KC-404 also inhibited the histamine-induced increase in Rrs. These effects of KC-404 were more potent than those of aminophylline. On the other hand, the dose of KC-404 tested caused an increase in heart rate, although the degree was moderate as compared with aminophylline. From the results obtained in this study, it is considered that the pyrazolopyridine derivatives, particularly KC-404, may be promising bronchodilators for the treatment of bronchial asthma.

Airway Resistance↗