Biomedical subjects

H Bergstrand

Publications and source records attributed to H Bergstrand.

At least 37 records · Page 2Linked to original sources

PubMed1986

Is there a functional heterogeneity among IgE-type mast-cell-sensitizing antibodies?

It has recently been established that mast cells display functional heterogeneity. The question then arises whether the IgE-type of antibody, which avidly binds to and thereby sensitizes mast cells and basophils for allergen-induced release of mediators, also expresses functional heterogeneity. In the present article we bring together several experimental observations, mainly from the rat system, which are difficult to explain unless one postulates that mast cell/basophil-sensitizing antibodies of the IgE-type are heterogeneous in their cell-binding properties.

Allergens↗

PubMed1986

Antigen-induced bronchial anaphylaxis in actively sensitized SD rats. Effects of glucocorticoid treatment.

We examined the effects of glucocorticosteroids (GCS) on antigen-induced bronchial anaphylactic reactions (BAR) in SD rats immunized with ovalbumin (OA) and alum. The animals were treated with vehicle, budesonide (BUD), dexamethasone (DEX), or hydrocortisone (HC) at various times before intravenous (i.v.) antigen challenge. The drugs were administered either intraperitoneally (i.p.) or intratracheally (i.t.); the BAR was elicited by a low or by a high challenge dose of antigen. A BAR elicited by a low challenge dose of antigen was reduced in a dose-dependent way by all GCS after i.p. administration; at 1 mg/kg, BUD and DEX significantly reduced BAR and at 50 mg/kg all three of the examined compounds inhibited the BAR by 50% or more. For BUD, maximum effect was recorded when it was given 12 h before test. There was only a slight variation in the inhibitory effects of the GCS with immunization conditions of test animals. I.t. instillation of the drugs did not markedly increase their inhibitory capacity as compared to i.p. administration. BAR elicited by a high antigen dose was at best marginally affected by the GCS when given either i.p. or i.t. Thus, antigen-induced airway reactivity in rats can be reduced by GCS treatment provided that this is performed sufficiently long before the test and that the challenge dose of antigen is not too high.

Acetophenones↗

PubMed1986

The glucocorticosteroid, budesonide, partially blocks histamine release from human lung tissue in vitro.

IgE-receptor dependent, but not A23187-induced, histamine release from passively sensitized chopped human lung tissue, or from a dispersed lung cell population obtained from the tissue after enzymatic digestion, is reduced after incubation overnight of cells/tissue with the glucocorticosteroid budesonide (10(-7) M). Since the inhibitory effect of budesonide is reduced in the continuous presence of diluted reagin-rich serum used for passive sensitization, but not in the presence of heat-inactivated serum, it is suggested that the glucocorticosteroid acts by reducing the binding of IgE-antibody to the target cell(s).

Antibodies, Anti-Idiotypic↗

PubMed1985

Effects of long-term treatment with low dose cimetidine on allergen-induced airway responses and selected immunological parameters in atopic asthmatics.

Twenty asymptomatic atopic asthmatics were treated with either cimetidine 100 mg orally (13 patients) or placebo (7 patients) once a day for 4 weeks. Bronchial challenges were performed with the pertinent allergen immediately before and 2 and 4 weeks after the initiation of treatment and, finally, 4 weeks after the cessation of treatment. Before each challenge blood was drawn for the determination of specific IgE antibody levels (RAST procedure) and total IgE (PRIST), allergen- and anti-IgE-induced basophil histamine release, and mitogen-induced lymphocyte (3H)-thymidine incorporation. Patients treated with cimetidine were found to be significantly (P less than 0.05) less responsive to bronchial allergen challenge during the treatment than before it; patients treated with placebo were more reactive (P less than 0.05) 14 days after the initiation of treatment. The difference in responsiveness to treatment between the placebo and the cimetidine groups was significant 14 days (P less than 0.01) and 4 weeks (P less than 0.05) after the initiation of treatment; no significant difference in allergen responsiveness was recorded between the groups 1 month after cessation of treatment. No clear-cut changes in specific IgE antibody or total IgE levels, histamine release capacity, or mitogen-induced lymphocyte responsiveness were observed in either group, except that lymphocytes from cimetidine-treated patients tended to show an increased ratio of PHA- to PMA-induced thymidine incorporation. Thus, it was found that the treatment of asymptomatic atopic asthmatics with low-dose cimetidine reduced their allergen sensitivity in bronchial provocation tests by a mechanism which remains to be elucidated.

Adult↗

PubMed1985

Modulatory effects of Freund's adjuvant treatment on mast cell histamine release and homocytotropic antibody synthesis.

The present study examines the influence of Freund's complete adjuvant (FCA) injections on sensitized PVG rats with respect to serum levels of IgE and IgG2 alpha antibodies and total IgE (all assessed by radioimmunoassays) and the capacity of serosal mast cells to release histamine on challenge in vitro with 'immunological' secretagogues (specific antigen, anti-IgE, concanavalin A) or with compound 48/80. The rats were immunized with 10 micrograms ovalbumin (OA); alum, Bordetella pertussis vaccine, or silica gel were employed as adjuvants. Treatment with FCA was performed by single intraperitoneal injections 3, 2, or 1 week(s) before or 1 or 2 weeks after sensitization. Tests were conducted 3 weeks after sensitization. The results show that the effect of FCA treatment varied reproducibly with the adjuvant employed for sensitization and with the timing of the FCA administration. FCA treatment could either increase, fail to affect, or decrease total serum IgE and OA-IgG2 alpha antibody levels as well as serosal mast cell responsiveness, whereas OA-IgE antibody responses were decreased or not affected. Moreover, serum levels of OA-IgE and OA-IgG2 alpha antibodies and total IgE were affected by FCA treatment independently of each other. Finally, serosal mast cell responsiveness to a given secretagogue could be influenced by the FCA treatment apparently independently of that to other secretagogues. A salient finding was that effects of FCA treatment on mast cell responsiveness did not necessarily conform to effects on antibody synthesis. Collectively, these data support the opinion that the mechanisms of action of the IgE-promoting adjuvants employed differ and suggest that the expression of serosal mast cell responsiveness to each examined secretagogue can be regulated separately. They also suggest that the serosal mast cell sensitizing capacity of homocytotropic antibodies may not be adequately quantified by immunochemical methods employing reagents prepared against IgE and IgG2 alpha protein.

Alum Compounds↗

PubMed1984

Anti-IgE-induced histamine release from rat tissues passively sensitized in vivo with myeloma IgE differs with strain and mast cell source.

Four different strains of rats, BDII, E3, LE, and OM/N, each with a low basal serum level of IgE, were examined with respect to anti-IgE- and ConA-induced release of histamine from serosal mast cells and chopped lung tissue. Tests were performed before and three days after i.p. injection of a graded dose of myeloma IgE (IR 162)-containing ascitic fluid. There was a clearcut strain difference in response capacity with respect to ConA- and anti-IgE-induced release of histamine from serosal mast cells before myeloma IgE-injection. Response capacity increased in some but not all strains after myeloma IgE injection; increase in response capacity of serosal mast cells did not correlate to that of chopped lung tissue. Analogous findings were observed when two of the strains, LE and E3, were passively sensitized by i.p. injection with serum containing another myeloma IgE (IR2). These results indicate that differences exist between mast cells of different rat strains, and within strain between mast cells of various tissues in capacity to become sensitized to myeloma IgE.

Animals↗

PubMed1984

Immunologically induced pleural and peritoneal mast cell histamine release: difference in responsiveness in relation to secretagogue and rat strain used.

Responsiveness was compared for cell populations harvested from the peritoneal and pleural cavities of rats with respect to histamine release induced by specific antigen, anti-IgE, and Con A. Cell populations were obtained from Fischer, PVG or Sprague-Dawley (SD) rats, which were either untreated or immunized with 10 micrograms ovalbumin together with 100 mg alum intraperitoneally. Mast cell histamine release was examined with crude cell populations. The results show that differences in response capacity to the various secretagogues employed do exist between pleural and peritoneal cells in Fischer and PVG strains but under the present circumstances apparently not in SD rats. These differences vary in magnitude with the secretagogue employed and (for cells from immunized animals) with the time elapsed between immunization and test. In PVG rats, neither pleural nor peritoneal mast cell histamine release induced by antigen paralleled serum OA-IgE antibody levels. Furthermore, an increase in anti-IgE induced release of histamine from serosal mast cells occurred in parallel with a decrease in total serum IgE levels. These data indicate that the functional differences observed with respect to release properties of the two cell populations are due not only to intrinsic differences in mast cell populations but also to differences in reaginic antibodies sensitizing the cells.

Animals↗

PubMed1984

Anti-IgE-and ConA-induced histamine release from human basophilic leukocytes: the existence of differences in relative responses within individuals.

Histamine release was induced from human blood leukocytes with Concanavalin A (ConA) and two different preparations of anti-IgE. A dose-response curve was constructed for each cell population and secretagogue. No qualitative difference in response pattern was observed with the two anti-IgEs; however, the relative release-inducing efficacy of ConA and anti-IgE seemed to vary with the individual providing the cells. These findings indicate that release induced by ConA is not completely equivalent to that induced by anti-IgE.

Antibodies, Anti-Idiotypic↗

PubMed1984

Inhibitory effect of glucocorticosteroids on anti-IgE-induced histamine release from human basophilic leukocytes: evidence for a dual mechanism of action.

Anti-IgE-induced histamine release from human leukocytes is inhibited when the cells before challenge are cultured overnight in the presence of glucocorticoids (GCSs). The present report suggests that the GCSs might exert their effect by at least a dual mechanism of action. Histamine release was induced by a suboptimum concentration of anti-IgE. When the release recorded in the presence of the steroid is plotted against the release recorded in its absence, the data points of several experiments fit a regression line characterized by two parameters: its slope and its intercept with the abscissa. Structure-activity examination with selected GCSs indicates that the orders of potency for affecting these two parameters are not identical. Furthermore, pulse experiments suggest that the cells require different times of contact with the steroid to express inhibition according to the two parameters. The removal of adherent cells or platelets did not markedly affect the degree of leukocyte histamine release or its inhibition by a given GCS, suggesting that the steroid interacts directly with the basophil. Finally, steroid-induced inhibition was not affected by the putative phospholipase A2-inhibitor p-bromophenacylbromide (BPB) or the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA).

Antibodies, Anti-Idiotypic↗

PubMed1984

Changes in bronchial anaphylactic reactivity induced in guinea-pigs by long-term treatment with histamine H2-agents.

Guinea-pigs were sensitized to ovalbumin (OA) by immunization regimens chosen to cause antigen-induced bronchial anaphylactic responses mediated mainly either by IgE-like antibodies or by IgG1-like antibodies. Treatment of the IgE-producing animals for three weeks with the histamine H2-receptor antagonist cimetidine (1 mg kg-1 i.p. once a day) or with the H2-agonist dimaprit (0.1, 1.0, or 10 mg kg-1 i.p. once a day) led to a significantly reduced bronchial response capacity compared with that of the saline-treated controls challenged intravenously with antigen one week after the end of treatment. The changes were biphasic and not strictly dose-dependent. In contrast, acute treatment of immunized animals with a single dose of cimetidine (10 or 30 mg kg-1 i.v.) or dimaprit (1 or 10 mg kg-1 i.v.) 2 min before challenge with OA did not significantly affect the bronchial anaphylactic response. However, long-term treatment with cimetidine (10 mg kg-1) or the dimaprit analogue, S-[4-(N, N-dimethylamino)-butyl] isothiourea (SKF Compound 91488) (1 mg kg-1), which is reported not to activate H2-receptors, had no effect on the response capacity. Treatment with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1) did not influence the response capacity to antigen challenge in IgG1- type animals. Dimaprit (1 mg kg-1) did not affect the responsiveness to intravenous provocation with histamine in 'IgE-type' animals. Antigen-induced release of histamine from chopped lung tissue in vitro was not significantly affected in 'IgE-type' animals treated with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1). Treatment of immunized animals with cimetidine or dimaprit one week before and one week after a booster injection of antigen also led to reduced response capacity compared with that of saline-treated controls. However, the serum levels of IgE-like homocytotropic antibodies of these animals were not reduced; on the contrary, those of IgG1-antibody were increased in dimaprit-treated animals. These data show that intermittent treatment with histamine H2-agents reduces reagin-mediated anaphylactic response capacity in vivo in actively sensitized guinea-pigs by an as yet undefined mode of action.

Anaphylaxis↗

PubMed1984

Bronchial anaphylaxis in actively sensitized Sprague Dawley rats: studies on mediators involved.

Previous experiments have shown that SD rats actively sensitized to ovalbumin (OA) undergo bronchial anaphylaxis at intravenous challenge with a specific antigen. The inhibitory effect of antiallergic drugs in this experimental system and the relation of the response to serum reaginic antibody levels, depend on sensitization conditions (Dahlbäck 1981; Dahlbäck et al. 1982). The present experiments indicate that the main primary mediators of the respiratory anaphylaxis are serotonin and product(s) of the cyclooxygenase pathway of arachidonic acid metabolism. This is the case whether the animals are sensitized with 10 or 100 micrograms OA together with 100 mg alum and whether they are examined 2-3 or 5-6 weeks after sensitization. However, the bronchoconstrictory efficacy of exogenously added 5-HT varies with the immunization conditions of the animals: those given 100 micrograms OA together with alum are more reactive to 5-HT at intravenous challenge than animals given 10 micrograms AO and alum. Moreover, compounds known to affect the lipoxygenase pathway of arachidonic acid metabolism influence the bronchial anaphylactic reaction in different ways depending on immunization and test conditions. These data suggest that 5-HT and some not yet identified product(s) of cyclooxygenase/thromboxane synthetase are main mediators of allergen-induced bronchial anaphylaxis in the rat and that products of the lipoxygenase pathway play a minor direct role but may modulate the response.

Acetylcholine↗

PubMed1983

Antigen-induced release of histamine from serosal mast cells, lung, and tracheal tissue: variation with tissue and rat strain in relation to serum IgE-antibody level.

Rats of the Brown Norway (BN)2, Fischer, PVG and Sprague Dawley (SD) strains were immunized intraperitoneally with graded doses of ovalbumin (OA) together with either alum or Silica gel. At specified times after immunization, in vitro histamine release from serosal mast cells and from chopped lung and tracheal tissue was determined after challenge with OA. The development of the capacity to respond in these tests seemed to vary within strain independently for mast cells, lung, and tracheal tissue with immunization dose of antigen and nature of adjuvant. These variations were not closely correlated to observed variations in serum levels of OA-IgE antibody or ratio OA-IgE to total IgE as determined by radioimmunoassay. Furthermore, variations between strains in response capacity did not correlate to inter strain variation in median serum OA-IgE antibody level. These results do not clearly conform to the possibility that one single class of IgE mediates anaphylactic reactivity of various tissues of the rat.

Animals↗

PubMed1983

The non-specific enhancement of allergy. II. Precipitation of anaphylactic in vitro response capacity and serum IgE and IgG2a antibody synthesis in primed but non-responding rats by injection of alum.

PVG rats given injections of 1 microgram ovalbumin (OA) together with 10 mg Silica gel failed to provide serosal mast cells or lung tissue with the capacity to release histamine on in vitro challenge with the antigen. However, if such animals were injected i.p. with 100 mg of alum (without any further antigen addition) 3-9 weeks after the primary antigen injection, their mast cells and lung tissue showed a clear-cut capacity to respond in vitro, when examined 1 week after the alum injection. Injection of only 15 mg alum did not induce such a response capacity. The fading of the reactivity induced by an alum injection could be prevented by a repeated injection of the adjuvant alone. Pretreatment of the rats with cyclophosphamide (33 mg/kg) 2 days before the primary antigen injection did not affect the response capacity induced by a booster injection 3 weeks later. S.c. injection of alum also precipitated response capacity in animals primed by i.p. injection of antigen and Silica gel. The anaphylactic response capacity induced by injection(s) of alum was generally accompanied by increased levels of OA-IgE and especially OA-IgG2a antibody; however, a clear-cut correlation between either serosal mast cell or lung tissue response capacity and serum OA-IgE or IgG2a antibody titer could not be demonstrated. These data show that in primed animals, which do not express allergic response capacity, such a capacity can be induced by injecting adjuvant alone, even several weeks after the primary antigen injection.

Aluminum Hydroxide↗

PubMed1983

The non-specific enhancement of allergy. III. Precipitation of bronchial anaphylactic reactivity in primed rats by injection of alum or B. pertussis vaccine: relation of response capacity to IgE and IgG2a antibody levels.

SD rats were sensitized by an i.p. injection of 1 microgram or 10 micrograms ovalbumin (OA) together with 10 mg Silica gel. At the indicated time after sensitization, allergic response capacity of the animals was estimated by measuring changes in intratracheal pressure induced by an i.v. injection of 0.3 mg OA (low challenge dose) or 5 mg OA (high challenge dose). Animals given 1 microgram OA in Silica gel showed no response capacity at 14, 35 or 47-48 days after sensitization. Animals injected with 10 micrograms OA showed a clear-cut response with a peak at 14 days; at 7 weeks after immunization the response capacity had faded almost completely. Specific OA-IgE antibody and total IgE serum levels were examined by radioimmunoassay. A slight increase in OA-IgE antibody was recorded in animals injected 14 days before test with 10 micrograms ovalbumin and Silica gel; animals given 1 microgram OA and Silica showed no OA-IgE antibody. Five weeks after sensitization, some animals of each group were injected i.p. with 100 mg alum, B. pertussis vaccine (2 ml of Perthydral), or saline, all injections being made without any further antigen addition. 12-13 days after such an injection, alum-treated animals showed high response capacity at bronchial anaphylactic tests and high OA-IgE antibody levels but comparably low levels of total IgE. Animals injected with B. pertussis, on the other hand, showed low response capacity (bronchial anaphylactic tests and OA-IgE antibody levels) but high total IgE-antibody levels. The bronchial anaphylactic response in the B. pertussis-injected animals but not the alum-injected animals was significantly correlated to serum IgG2a antibody levels. These results show that injection of alum or B. pertussis vaccine without antigen can precipitate/enhance anaphylactic response capacity and production of specific and non-specific IgE and IgG2a.

Adjuvants, Immunologic↗

PubMed1982

Anti-IgE and Con A-induced histamine release from mast cells of four rat strains: correlation with total serum IgE.

Anti-IgE- and Con A-induced histamine release from serosal mast cells were compared to each other and to total serum levels of IgE in non-immunized, alum-injected, and Silica gel-injected rats of the BN, Fischer, PVG, and SD strains. The results indicate that the degree of anti-IgE- and Con A-induced release is strain-dependent and varies with immunization conditions. Furthermore, there is a gross but not complete correlation between the degree of serosal mast cell histamine release induced by the two secretagogues. However, Con A- or anti-IgE-induced release could significantly be correlated to serum levels of total IgE only in the Fischer strain but not in the BN or the PVG strains. In the SD strain, Con A-induced release correlated to serum IgE levels in Silica gel-injected but not in alum-injected animals.

Animals↗

PubMed1982

Anti-IgE-induced histamine release from human basophilic leukocytes: inhibition depends on nature and concentration of inhibitor and secretagogue.

Histamine release from human basophilic leukocytes was induced by increasing concentrations of anti-IgE in the presence of various concentrations of 2-deoxyglucose (2-DOG), the histamine H2-receptor agonist dimaprit, theophylline, or enprofylline (a new antiasthmatic xanthine derivative). The results show that the degree of inhibition produced by each agent differed with the concentration of anti-IgE used and with the nature and concentration of the inhibitor. These data indicate that great care should be used when characterizing an inhibitor of mediator release by simply giving a figure for the per cent inhibition of release observed in its presence.

Antibodies, Anti-Idiotypic↗

PubMed1982

Relation between bronchial reactivity to antigen in vivo and serum IgE and IgG2a antibody levels in rats.

Sprague Dawley rats were immunized with graded doses of ovalbumin (OA) together with alum. The capacity of the animals to produce a bronchial anaphylactic response to intravenous antigen challenge was related to serum OA-IgE and OA-IgG2a antibody levels estimated by radioimmunoassay. A significant correlation between bronchial anaphylactic response capacity and OA-IgE antibody levels was found under a few, but not all, of several carefully chosen experimental conditions. No correlation was demonstrable between the in vivo reactivity of the animals and their serum levels of OA-specific IgG2a antibodies.

Anaphylaxis↗

PubMed1982

Antigen-induced release of histamine from rat tissues in vitro: dissociation in development of serosal mast cell, lung tissue, and tracheal tissue response capacity.

We examined the temporal development and the fading in Sprague Dawley rats, actively sensitized to ovalbumin (OA), of the capacity of serosal mast cells, chopped lung tissue, and occasionally chopped tracheal tissue, to respond at antigen challenge in vitro with histamine release. Response capacity of both serosal mast cells and lung tissue developed within 2-3 weeks after injection of 1 microgram OA or more together with 100 mg of alum. Maximum response capacity was observed in cells and tissue from animals injected with 10 micrograms OA, part of the response capacity then remained until 3 months after immunization. Development of serosal mast cell reactivity was occasionally dissociated from that of lung tissue. When low amounts of alum (1 or 10 mg) were employed as adjuvant, lung tissue reactivity could be induced in the virtual absence of serosal mast cell response capacity. Silica gel was less efficient than alum as an adjuvant for induction of a primary response, but 'secondary' tissue responses could be induced when silica gel was used as an adjuvant. Pretreatment of the animals with cyclophosphamide before the booster injection enhanced and prolonged the response capacity of lung tissue. Animals injected with OA together with Freund's complete adjuvant did not provide responding serosal mast cells; response capacity of lung tissue varied with immunization dose of antigen. Antigen-induced histamine release from chopped tracheal tissue did not correlate to response capacity of lung tissue. Thus, the development in the rat of response capacity with respect to antigen-induced histamine release dissociates from serosal mast cells, lung tissue, and tracheal tissue.

Adjuvants, Immunologic↗