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Biomedical subjects

B J Undem

Publications and source records attributed to B J Undem.

At least 109 records · Page 6Linked to original sources
PubMed1989

Dexamethasone does not inhibit the release of mediators from human mast cells residing in airway, intestine, or skin.

Glucocorticoids are potent anti-inflammatory drugs that are widely used in the treatment of allergic disorders. Their actions are often species specific or cell-type specific. Previous studies have demonstrated that glucocorticoids inhibit mediator release from mast cells derived from the peritoneum of mouse or rat and from guinea pig lung, but not those residing in human lung parenchymal tissue. In the present study, we have analyzed the effect of overnight culture with dexamethasone (10(-6) to 10(-7)M) on the subsequent IgE-dependent release of mediators from human mast cells derived from airway tissue, intestine, and skin. Airway tissue was passively sensitized with antigen-specific, IgE-rich serum during the culture period and subsequently challenged with ragweed antigen E. Skin and intestinal mast cells were challenged with anti-IgE. Histamine and immunoreactive LTC4 and PGD2 release was monitored in all experiments. Prostaglandin E release was quantitated in the experiments using airway tissue. Dexamethasone treatment failed to inhibit the release of mast cell mediators from all three tissues, but it inhibited the antigen-induced release of immunoreactive PGE from other cells residing in airway tissue. These results confirm earlier studies of the effects of glucocorticoids on human lung parenchymal mast cells, but contrast with the inhibitory effects of steroids observed in murine mast cells and human basophils.

Adult↗
PubMed1989

Influence of electrical field stimulation on antigen-induced contraction and mediator release in the guinea pig isolated superfused trachea and bronchus.

These studies examined the ability of electrical field stimulation (EFS) to influence antigen-induced responses in the guinea pig isolated trachea and main-stem bronchi. Airways isolated from guinea pigs actively sensitized to ovalbumin were superfused and stimulated transmurally with square pulses of 1 msec duration at a frequency of 16 pulses per sec. In the trachea, EFS caused an atropine-sensitive contraction followed by a maintained relaxation. The relaxation consisted of adrenergic and nonadrenergic components. In the bronchus, EFS caused a maintained contraction. This contraction was due to a combination of cholinergic (atropine-sensitive) and noncholinergic (capsaicin-sensitive) mechanisms. Histamine could not be detected in superfusate samples during electrical stimulation alone of either the trachea or bronchus. EFS significantly inhibited ovalbumin-induced tracheal contractions by about 30% without altering ovalbumin-induced histamine or immunoreactive peptido-leukotriene release from the tissues. EFS had a similar inhibitory effect on the contraction induced by application of exogenous histamine (10(-5) M). The electrical stimulus-induced inhibition of the antigen-induced contraction was abolished by tetrodotoxin and propranolol and reduced by a combination of atropine, propranolol and phentolamine. Norepinephrine (5 x 10(-6) M) inhibited ovalbumin-induced histamine release by about 30% without altering the contraction. Carbamylcholine had no effect on ovalbumin-induced histamine release. In the guinea pig bronchus, EFS stimulation had no effect on either histamine release or contraction induced by ovalbumin. These results demonstrate that in the guinea pig trachea nerve stimulation can significantly antagonize antigen-induced contractions and suggest that this is due to a functional antagonism by adrenergic and nonadrenergic relaxant neurotransmitters at the level of the airway smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of removal of epithelium on antigen-induced smooth muscle contraction and mediator release from guinea pig isolated trachea.

We examined the effect of removal of the epithelium on antigen-induced smooth muscle contraction and the release of mediators of inflammation from superfused, sensitized guinea-pig tracheal spirals in vitro. The epithelium was stripped from one-half of each trachea by mechanical means, and immunologic responses were evaluated by paired analysis. Removing the epithelium potentiated antigen-induced contraction, as reflected by a 5-fold leftward shift in the antigen dose-response curve, but the maximum response to antigen was not altered. This potentiation was not inhibited by pretreating the tissues with indomethacin (5 X 10(-6) M). At maximum concentrations of antigen removing the epithelium had no effect on the magnitude or kinetics of release of immunoreactive sulfidopeptide leukotrienes, prostaglandin (PG) D2, PGF2 alpha or thromboxane B2. Removing the epithelium did, however, significantly decrease the release of PGE and 6-keto-PGF1 alpha, a prostacyclin metabolite. Antigen-induced histamine release was enhanced by removing the epithelium; this effect varied inversely with antigen concentration. Selectively exposing either the luminal or serosal surface of an intact, superfused trachea to antigen resulted in the release of less than 5% of the total tissue histamine. Removing the epithelium from the intact trachea increased histamine release to approximately 25% following luminal but not serosal exposure to antigen. These studies demonstrate that the tracheal epithelium can act to inhibit antigen-induced airway contraction in vitro. This may in part reflect the role of the intact epithelium as a diffusion barrier which can limit the rate of influx of antigen molecules and thereby influence tissue mast cell activation.

Animals↗
PubMed1988

Isoproterenol-induced inhibition of immunoglobulin E-mediated release of histamine and arachidonic acid metabolites from the human lung mast cell.

The inhibitory effect of isoproterenol was examined on the release of histamine, leukotriene C4 (LTC4), and prostaglandin D2 (PGD2) from human lung mast cells. Isoproterenol was more potent in inhibiting anti-immunoglobulin (Ig) E-induced LTC4 and PGD2 release than histamine release from the dispersed lung cell preparations (2-5% mast cells). The negative log molar EC50 values of isoproterenol for inhibiting histamine, LTC4 and PGD2 release were 8.2 +/- 0.2, 8.9 +/- 0.2 and 8.7 +/- 0.3, respectively (mean +/- S.E.M., n = 8). Isoproterenol seldom inhibited histamine release by more than 60%, but usually abolished the release of LTC4 and PGD2. The potency of propranolol (KB = 6 X 10(-10) M) was the same for competitively antagonizing isoproterenol mediated inhibition of histamine, LTC4 or PGD2 release. Using the irreversible beta adrenergic receptor antagonist, bromoacetylalprenololmenthane, the estimated dissociation constant of isoproterenol was 2 X 10(-7) M irrespective of whether inhibition of anti-IgE-induced histamine or LTC4 release was examined. When the divalent cation ionophore A23187 was used to induce histamine release, isoproterenol had either no effect or potentiated the release. In contrast, isoproterenol was capable of virtually abolishing A23187-induced LTC4 release. Qualitatively similar effects of isoproterenol were observed on purified mast cell preparations (greater than 80% mast cells); however, the potency of isoproterenol in inhibiting mediator release from these preparations was reduced. The results demonstrate that there is a substantial receptor reserve for isoproterenol-mediated inhibition of histamine, LTC4 and PGD2 release from the human lung mast cell. The intrinsic efficacy of isoproterenol in inhibiting anti-IgE-induced release of arachidonic acid metabolites is approximately 3 times greater than that for inhibiting histamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprenolol↗
PubMed1988

An analysis of the functional interactions of selected contractile agonists in the guinea pig isolated trachea.

Functional interactions between several contractile agonists were examined in the guinea pig isolated trachea. Cumulative concentration-response effects of agonist A were obtained in the absence and presence of steady-state contractions induced by agonist B. The agonists examined included histamine, prostaglandin D2, platelet activating factor, leukotrienes E4 and D4 and carbamylcholine. We found that none of the agonists studied caused a leftward shift in the concentration-response curve of a second agonist, nor did any agonist decrease the concentration of a second agonist required to evoke a maximum response. In general the functional interactions fit the predictions based on the early models of functional additivity. However, the interactions deviated categorically from this model in that there was less than predicted additivity at concentrations of the interactants that alone induced greater than a 50% response. The degree to which this deviation occurred was agonist dependent. The results suggest that in the guinea pig trachea a contractile agonist does not uncover or increase a reserve in the receptor-subeffect-response chain of a second contractile agonist. The findings that the quantitative nature of the interactions were somewhat agonist dependent supports the hypothesis that more than one biochemical mechanism is involved in the receptor-mediated contraction of airway smooth muscle.

Algorithms↗
PubMed1987

Antigen-induced sulfidopeptide leukotriene release from the guinea pig superfused trachea.

The effect of antigen (ovalbumin) challenge on smooth muscle contraction and release of sulfidopeptide leukotrienes and histamine from superfused, actively sensitized guinea pig trachea was examined. Maximum concentrations of ovalbumin caused the release of 16 +/- 4 ng/g immunoreactive sulfidopeptide leukotriene (i-LT) and 27 +/- 3% of the endogenous histamine (x +/- S.E.M., n = 19). High performance liquid chromatography combined with a sulfidopeptide leukotriene radioimmunoassay was used to demonstrate that on a molar basis, approximately 10% of the leukotriene immunoreactivity recovered was LTC4, 45% LTD4 and 45% LTE4. Indomethacin slightly increased ovalbumin-induced histamine release and substantially enhanced (3-fold) i-LT release from the trachea. Neither the profile nor rate of sulfidopeptide leukotriene release was altered by indomethacin. Indomethacin had no effect on the maximum amplitude of the antigen-induced contraction but significantly enhanced the magnitude of contraction observed after 10 min of antigen exposure. These results demonstrate that actively sensitized airways synthesize and release sulfidopeptide leukotrienes upon challenge with specific antigen and that endogenously formed LTC4 is efficiently metabolized to LTD4 and LTE4. The results with indomethacin support the hypothesis that indomethacin potentiates antigen-induced airway contraction in vitro by enhancing the release of mast cell associated mediators.

Animals↗
PubMed1987

Antigen- and histamine H1 receptor-mediated relaxation of guinea pig isolated trachea.

We have investigated the effect of challenge in vitro with specific antigen (ovalbumin) on actively sensitized guinea pig tracheal rings maximally precontracted with methacholine. Ovalbumin relaxed the trachea in a concentration-dependent fashion with a negative log ED50 value (g/ml) of 7.0 +/- 0.3. In 16 experiments, the maximum antigen-induced relaxation was 26 +/- 3% of complete relaxation induced by 10(-3) M papaverine (mean +/- S.E.M.). Antigen-induced relaxations were selectively antagonized by diphenhydramine. Similarly, histamine relaxed the precontracted tracheal smooth muscle with a negative log molar ED50 of about 4.5 and a maximum effect of 28 +/- 3% (mean +/- S.E.M., n = 20). Histamine-induced relaxations were antagonized by diphenhydramine and mepyramine but were unaffected by cimetidine, metiamide or burimamide. Dimaprit (10(-5)-10(-3) M) did not relax the precontracted trachea. Indomethacin significantly inhibited relaxation induced by both antigen and histamine. In contrast, phenidone or 5,8,11,14-eicosa-tetraynoic acid had no effect on relaxation but reversed the inhibition by indomethacin. Neither propranolol (10(-6) M) nor removing the tracheal epithelium inhibited histamine-induced relaxation. These results suggest that antigen-induced relaxation of guinea pig tracheal smooth muscle involves activation of histamine H1 receptors and can occur independently of arachidonic acid metabolism, beta-adrenoceptor activation or airway epithelium.

Animals↗
PubMed1987

The effect of indomethacin on immunologic release of histamine and sulfidopeptide leukotrienes from human bronchus and lung parenchyma.

We studied the effect of indomethacin on immunologic mediator release from human bronchial tissue (n = 6) and lung parenchyma (n = 7). Tissues were obtained from surgical specimens, minced, passively sensitized, and challenged with antigen E or anti-IgE in the presence or absence of indomethacin. At maximal levels of immunologic stimulation with either antigen or anti-IgE, the bronchial and parenchymal tissues released approximately 5 and 20% of total histamine (net), respectively, and approximately 3.5 and 45 ng/g of immunoreactive sulfidopeptide leukotriene, respectively. Analysis by high performance liquid chromatography followed by radioimmunoassay revealed that the airway supernatants contained LTD4 and LTE4, whereas the lung parenchymal samples contained predominantly LTE4. Little or no LTC4 was detected in either airway or parenchymal samples. Incubation with indomethacin (5 x 10(-6) M) resulted in approximately a 3-fold increase in antigen or anti-IgE-induced release of leukotrienes from the bronchial tissue. Indomethacin also enhanced antigen-induced histamine release approximately 2-fold but had no effect on anti-IgE-induced histamine release from this tissue. In contrast, indomethacin had no effect on antigen or anti-IgE-induced histamine or leukotriene release from the lung parenchymal tissue at any level of immunologic stimulation. These results support the hypothesis that indomethacin enhances human anaphylactic bronchospasm in vitro through an increase in mediator release from bronchial mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1987

Dexamethasone inhibits the antigen-induced contractile activity and release of inflammatory mediators in isolated guinea pig lung tissue.

Treatment for 24 h in vitro with dexamethasone inhibited the antigen-induced contractile response in guinea pig tracheal rings and parenchymal strips without inhibiting the contractile response of the tissues to either methacholine or histamine, respectively. Antigen-induced histamine release was inhibited by approximately 50% in both tissues by prior treatment with dexamethasone. Dexamethasone treatment also inhibited the release of immunoreactive sulfidopeptide leukotriene from parenchymal strips. In tracheal rings, dexamethasone treatment reduced spontaneous release of all cyclooxygenase metabolites (PGE2, PGF2 alpha, TXB2, PGD2, and 6-k-PGF1 alpha were tested), with the exception of PGD2, and also inhibited the antigen-induced release of all cyclooxygenase metabolites studied. Dexamethasone-treatment did not inhibit the spontaneous release of cyclooxygenase metabolites in the guinea pig lung strips, and only modestly inhibited the antigen-induced release of PGE2, PGF2 alpha, and PGD2. The results suggest that the inhibition of contractile response of guinea pig lung strips and airway tissue to antigen by dexamethasone is the result of a reduced release of inflammatory mediators. The inhibition by dexamethasone of antigen-induced release of mast cell mediators from guinea pig lung parenchyma contrasts with results previously obtained with human parenchymal lung tissue.

Animals↗
PubMed1987

Immunological regulation of synaptic transmission in isolated guinea pig autonomic ganglia.

We have attempted to identify a role for mast cells in autonomic ganglia by examining the effects of antigen challenge on mast cell-associated mediator release and synaptic transmission through the superior cervical ganglion isolated from ovalbumin-sensitized guinea pigs. Ovalbumin induced the release of 7.9 ng of histamine, 40 pg of immunoreactive sulfidopeptide-leukotriene, and 140 pg of immunoreactive-PgD2 per ganglion. Ovalbumin produced long-lasting potentiation (51 +/- 4%, mean +/- SEM, n = 66) of synaptic transmission, the protracted nature of which could not be mimicked by exogenous histamine (10(-5) M). Selective histamine H1 antagonists inhibited the antigen-induced potentiation, but did not reverse it when added any time after antigen exposure. These results indicate that immunologic activation of mast cells can directly potentiate neurotransmission in sympathetic ganglia. Histamine appears to be a mediator involved in the induction of antigen-induced potentiation of synaptic transmission, but alone cannot account for the long term nature of this phenomenon.

Animals↗
PubMed1986

Comparative studies of mediator release from guinea pig lung mast cells and basophils.

Guinea pig lung mast cells and blood basophils were isolated and purified and their mediator release characteristics were compared. Upon stimulation with the antigen ovalbumin (OA) of cells passively sensitized with antiovalbumin (anti-OA) antibody, both cell types released histamine. The sensitivity and maximal response (20 to 25% histamine release) to OA was similar for both cells and was unaffected by cell purification. Antigen-induced histamine release (HR) was dependent upon added calcium to a similar extent (1 mM Ca++ maximal release) in both cell types; OA stimulation of passively sensitized mast cells also released leukotriene bioactivity (maximal release, 52 +/- 7 units/10(6) mast cells). There was no correlation between OA-induced leukotriene release and mast cell purity. No leukotriene bioactivity was detected in actively (sheep blood sensitization) or passively (anti-OA) sensitized basophils. Both lung mast cells and blood basophils released histamine in response to the secretagogues calcium ionophore A23187 and 12-O-tetradecanoylphorbol-13-acetate (TPA); TPA-induced HR from mast cells was independent of added calcium. In basophils, TPA-induced HR was only partially independent of added calcium. While both cell types were poorly responsive to the secretagogue 48/80, only the lung mast cell demonstrated inconsistent HR to concanavalin A (Con-A). Phosphatidylserine had no effect on HR provoked by antigen, Con-A, or compound 48/80. These observations demonstrate similarities and differences in mediator release characteristics between guinea pig lung mast cells and blood basophils that are similar to those observed with human lung mast cells and basophils. These observations also suggest a lack of influence on mediator release by other cell types present in dispersed lung cell and mixed leukocyte preparations.

Animals↗
PubMed1986

Effects of forskolin alone and in combination with isoproterenol on antigen-induced histamine release from guinea-pig minced lung.

Forskolin inhibited antigen-induced release of histamine and leukotrienes from minced guinea-pig lung. The apparent potency of forskolin was similar for the two measured responses. Combination of forskolin with isoproterenol resulted in an additive inhibition of histamine release. The results support the contention that increases in cyclic AMP can inhibit antigen-induced histamine release, but a two-site model for forskolin does not appear to be operative in this system.

Animals↗
PubMed1985

A procedure for isolation and partial purification of guinea pig lung mast cells.

Pulmonary mast cells were obtained from guinea pig lung using a combination of enzymatic digestion of tissue, centrifugal elutriation, and density gradient centrifugation on Percoll. In the initial procedure, lung tissue was enzymatically digested with collagenase and elastase in four 30 min incubations. Typically, monodispersed cell suspensions contained 4% mast cells. Further purification of these lung mast cells using elutriation and Percoll gradients consistently yielded mast cells of 40-78% (mean 51%) purity. These cells were morphologically intact, viable and found to be functional as determined by histamine release evoked by antigen and anti-guinea pig IgG1 antibody.

Animals↗
PubMed1985

Studies on beta-adrenoceptors of purified mast cells from guinea-pig lung.

Ovalbumin-induced histamine release from passively sensitized monodispersed cells (2-4% mast cells) or purified mast cells (50-78%) from guinea-pig lung was inhibited by isoproterenol and sulfonterol and their relative potencies or maximum responses were similar in both cases. The apparent dissociation constant for butoxamine was also independent of mast cell purity. The results indicate that beta-adrenoceptors mediating histamine release inhibition from lung are localized to mast cells and act independently of other cell types.

Animals↗
PubMed1985

Smooth muscle contraction and release of histamine and slow-reacting substance of anaphylaxis in pulmonary tissues isolated from guinea pigs passively sensitized with IgG1 or IgE antibodies.

In previous studies, we have provided evidence that different Fc receptors mediate antigen-induced pulmonary smooth muscle contractile responses after passive sensitization of guinea pigs with IgG1 or IgE antibodies. In this study, we examined the relationship between contraction and release of histamine and slow-reacting substance of anaphylaxis (leukotrienes) in superfused trachea and parenchymal strips as well as mediator release from minced lung fragments after passive sensitization of guinea pigs with IgG1 or IgE antibodies. Guinea pigs were immunized to produce either IgG1 or IgG1 and IgE using oxazolone-guinea-pig albumin or oxazolone-Ascaris plus cyclophosphamide, respectively. The contaminating IgG1 in the IgE-rich serum was removed by passage over a protein A-Sepharose column. Normal guinea pigs were passively sensitized intraperitoneally or intravenously with injections of either IgG1 or IgE 1 or 2 days before in vitro studies. Superfused tissues were challenged with 10(-1) mg/ml antigen (oxazolone-human serum albumin conjugate), and contractions and histamine and leukotriene release were monitored at discrete time intervals thereafter. At equivalent levels of contraction, substantially more histamine and leukotrienes were released from tissues taken from IgG1-sensitized animals. The amounts of histamine released from lung parenchymal strips and trachea in the IgE-sensitized state were approximately 5 and 38%, respectively, of those released from corresponding tissues in the IgG1-sensitized state. The leukotriene release from tissues isolated from IgE-sensitized animals was less than 4% of that released from tissues in the IgG1-sensitized state. Similar differences in mediator release were seen in comparable studies on minced lung fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of isoproterenol on histamine release induced from monodispersed guinea-pig lung cells by different secretagogues.

The effects of isoproterenol on histamine release induced by specific antigen (ovalbumin), a calcium ionophore (A23187) and a phorbol ester 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (TPA) were examined using passively sensitized, monodispersed guinea-pig lung cells containing 2 to 5% mast cells. Ovalbumin evoked histamine release in a manner dependent on added calcium. Isoproterenol inhibited this release and the inhibition was not overcome by increasing the concentration of calcium. The small amount of histamine release above spontaneous release induced by ovalbumin in the absence of added calcium was not altered by isoproterenol. Incubating the cells with ovalbumin in the absence of added calcium resulted in a time-dependent desensitization of histamine release induced by subsequent exposure to calcium. Isoproterenol did not affect either the rate or the maximum magnitude of antigen desensitization. Antigen-induced histamine release at maximum desensitization was not inhibited by isoproterenol. A23187 induced histamine release in a manner dependent on added calcium. This dependency was inversely related to the concentration of A23187. Isoproterenol had no affect on either the rate or magnitude of histamine release by A23187 regardless of the concentration of added calcium. TPA evoked histamine release in a manner independent of added calcium. Isoproterenol did not alter the rate or magnitude of histamine release induced by TPA. Both forskolin (10(-5) M) and dibutyryl cyclic AMP (10(-3) M) inhibited ovalbumin-induced histamine release, but neither substance altered A23187-induced release. Forskolin also failed to alter TPA-induced histamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evidence that only one type of beta adrenergic receptor mediates inhibition of antigen-induced histamine release from guinea-pig minced lung.

Lungs obtained from guinea pigs actively sensitized to ovalbumin were minced and prepared for histamine release studies. The effects of selective beta adrenergic receptor agonists and antagonists on the ovalbumin dose-response curve for histamine release were quantified. Beta agonist dose-response curves for inhibiting histamine release evoked by low, medium and maximum antigen concentrations as well as for shifting the antigen dose-response curve to the right were obtained. All experiments were conducted in the presence of phenoxybenzamine, 5,8,11,14-eicosatetraynoic acid and tissues were taken from reserpine-pretreated animals. The beta agonists isoproterenol and sulfonterol inhibited antigen-induced histamine release, whereas the beta-1 selective agonist, ICI 118587, had no effect at concentrations up to 10(-5) M. The beta-1 selective agonist R0363 inhibited histamine release only at concentrations known to activate the beta-2-type receptor. The maximum responses and potencies of isoproterenol and sulfonterol were inversely related to the concentration of ovalbumin at which the response was measured. The -log molar ED50 values of isoproterenol and sulfonterol were decreased approximately 10- and 5-fold, respectively, by increasing the antigen concentration from 10(-3) to 1 mg/ml. Therefore, the potency of sulfonterol relative to isoproterenol changed with antigen concentration. The beta antagonists propranolol, butoxamine and practolol did not alter antigen-induced histamine release when incubated with the tissue for 60 min. Apparent dissociation constants (KB) for propranolol and butoxamine were independent of the concentration of antigen used to provoke histamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗