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At least 1,531 records · Page 85Linked to original sources
PubMed1983

Basophil and mast cell degranulation: ultrastructural analysis of mechanisms of mediator release.

During anaphylactic degranulation, basophilic leukocytes and mast cells stimulated by specific antigen or other appropriate agents rapidly undergo a series of ultrastructural alterations that expose the contents of their cytoplasmic granules to the external milieu. This noncytolytic process results in the release of several potent inflammatory mediators whose combined local and systemic effects largely determine the clinical manifestations of allergic disorders of immediate hypersensitivity. In this report we briefly review our ultrastructural studies of anaphylactic degranulation in basophils purified from the peripheral blood of guinea pigs and humans and in mast cells purified from human lung.

Anaphylaxis↗
PubMed1980

Ultrastructural features of basophil and mast cell granulopoiesis in blastic phase Philadelphia chromosome-positive leukemia.

Ultrastructural and ultracytochemical studies were performed on blood and bone marrow specimens from 18 patients with Philadelphia chromosome-positive blastic leukemia; 7 patients were in blast transformation following a typical history of chronic myelogenous leukemia and 11 patients presented with "acute leukemia." The patients were divided into 2 morphologic groups on the basis of light microscopic and cytochemical observations. In group I, which consisted of 11 patients, the proliferating cells were "lymphoid" in appearance and demonstrated many cytochemical, biochemical, and immunologic features similar to those of the lymphoblasts of non-T, non-B acute lymphoblastic leukemia. In group II, which consisted of 7 patients, the proliferating cells were myeloid in appearance. On the basis of ultrastructural observations, the 11 group I patients were divided into 2 subgroups, A and B. Subgroup IA, consisting of 5 patients, was characterized by blasts that demonstrated no differentiating features. In subgroup IB, consisting of 6 patients, 20-30% of the leukemic cells contained inclusions that resembled leukemic mast cell or basophil granules. The leukemic cells in the 7 group II patients manifested myeloid characteristics by light microscopy and prominent basophil and mast cell granulopoiesis by electron microscopy. Abnormalities of other myeloid cell lines were also observed in both the lymphoid and myeloid groups of patients.

Basophils↗
PubMed1980

[Use of the basophil degranulation test and the leukocyte migration inhibition test to characterize mycogenic sensitization].

The results of experiments in using the basophil degranulation test and the leukocyte migration inhibition test for the characterization of mycogenous sensitization are presented. The model of mycogenous sensitization was created in guinea pigs by 3 injections of homogenized Candida albicans cells. Immediate allergic reaction is shown to develop earlier, as indicated by the results of the determination of homocytotropic antibody tites in passive skin anaphylaxis and by the results of the basophil degranulation test, than the appearance of delayed hypersensitivity detected by the leukocyte migration inhibition test.

Allergens↗
PubMed1982

Comparison of the receptors for IgE of various rat basophilic leukaemia cell lines. II. Studies with different anti-receptor antisera.

Receptors for IgE of rat basophilic leukaemia (RBL) cells, maintained in different laboratories were isolated by means of various anti-receptor antisera, and characterized by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis. Most antisera were shown to react with a receptor designated H and which, as shown previously, could be isolated by IgE-Sepharose but not by a combination of IgE and anti-IgE. Only two highly purified anti-receptor antibody preparations, which had been purified by adsorption to and elution from rat basophilic leukaemia cells, reacted primarily with a second kind of receptor molecule which had previously been designated R. Some indirect evidence was obtained which suggests that H is a highly immunogenic molecule. It was confirmed that the apparent molecular weight of H-like molecules varied on different RBL cell lines.

Animals↗
PubMed1982

Acute nonlymphocytic leukemia with basophilic differentiation.

Four cases of acute nonlymphocytic leukemia with primitive basophilic differentiation are presented. In all four cases, study revealed Philadelphia chromosome negativity, and in none were there clinical findings of chronic granulocytic leukemia. In each case, the leukemic blasts contained granules that failed to stain for peroxidase content but stained positively with toluidine blue. The former result could have led to the misclassification of the cases as lymphoid leukemias. Three of the four patients had physical findings that may have been due to circulating histamine excess. The histochemical and clinical features of these cases suggest that certain examples of leukemia with basophilic differentiation represent a distinctive variant of acute nonlymphocytic leukemia.

Acute Disease↗
PubMed1977

Blocking of histamine release from human basophils in vitro by the ATPase inhibitor, ethacrynic acid.

Ethacrynic acid, a known inhibitor of both Na+--K+ and Mg2+-activated ATPases, effectively inhibits histamine release from antigen-challenged human basophils in vitro. Ouabain, an inhibitor specific for Na+--K+-activated ATPases, shows no effect upon the quantity of histamine released from the antigen-challenged basophils. Ethacrynic acid also effectively inhibits Ca2+--ionophore A23187-induced release, implying it inhibits the Ca2+-dependent secretory stage of the histamine-release process. Inhibition of ATPases and histamine release by ethacrynic acid both require the presence of the olefinic bond in the ethacrynic-acid molecule. Possible utilization of analogues of ethacrynic acid as anti-allergic drugs and as a device to investigate the ATPase system of histamine-releasing cells is suggested.

Adenosine Triphosphatases↗
PubMed1978

Activation of human platelets by platelet activating factor (PAF) derived from sensitized rabbit basophils.

Rabbit basophil-derived platelet activating factor (PAF), a mediator of anaphylaxis, induces the aggregation and release of serotonin from rabbit platelets. In the present study, we report that PAF obtained by challenge of specifically sensitized rabbit basophils induced the noncytotoxic release of serotonin from human platelets; maximal extent of release ranged between 34-46%. This release was unaltered in the presence of indomethacin, indicating that such secretion was not a consequence of contaminating arachidonic acid; further, as previously demonstrated with platelets of rabbit origin, it was markedly independent of a requirement for an intact prostaglandin biosynthetic pathway. In contrast to its effect upon rabbit platelets, rabbit PAF did not induce aggregation of human platelets, suggesting that the aggregation and secretion reactions induced by this agent are separable and that this cross-species activation may be incomplete. Whether this is a result of the differential ability of rabbit PAF to bind to and activate rabbit as compared to human platelets or to the existence of a family of PAF molecules is not yet known. The capacity of PAF to participate in a secretory event involving human platelets lends support to the belief that PAF may play an important ubiquitous role in the cooperative, leucocyte-dependent, release of vasoactive amines which results in increased vascular permeability.

Animals↗
PubMed1980

Larger oligomers of IgE are more effective than dimers in stimulating rat basophilic leukemia cells.

The relative activity of rat IgE oligomers in eliciting secretion from mast cells and tumor basophils was examined using stable oligomers prepared by cross-linking IgE with dimethyl suberimidate. Oligomers were tested in vivo using passive cutaneous anaphylaxis (PCA) and in vitro by measuring their capacity to induce histamine release from normal rat mast cells and [3H]-5-hydroxytryptamine release from rat basophilic leukemia (RBL) cells. The PCA results confirmed previous work that showed no large differences in the activity of dimers, trimers, and higher oligomers of IgE. The same was also true with normal rat mast cells; however, the RBL cells sharply discriminated between the variously sized oligomers. The stimulatory activity of all oligomers on the RBL cells was enhanced by D2O. The findings imply that the manner by which the clustering of the receptors for IgE leads to generation of signals in RBL cells involves a mechanism capable of discriminating between a variety of polymeric states of the receptors. In addition, our results suggest that no more than a few hundred trimers or an even smaller number of higher oligomers are capable of inducing a considerable amount of secretion from these cells.

Animals↗
PubMedDate not supplied

Influence of salmeterol, a long-acting beta 2-adrenoceptor agonist, on IgE-mediated histamine release from human basophils.

Salmeterol, a long-acting beta 2-adrenoceptor agonist, prevents early and late asthmatic responses in atopic asthmatics and inhibits the release of inflammatory mediators from various cells and tissues. We investigated the effect of salmeterol on in vitro basophil histamine release (BHR). Washed basophil leukocytes from allergic (n = 6) and nonallergic subjects (n = 18) were preincubated for 10 min with different concentrations of salmeterol prior to stimulation with antigens (Ag) and anti-IgE for 45 min. BHR was detected by an automated fluorometric assay. If control BHR (without inhibition) reached > or = 30% of the total histamine content, maximal % inhibition (Imax, mean +/- SEM) and the concentration of salmeterol causing 30% inhibition (IC30, geometric mean) were calculated. At concentrations of between 1 and 100 microM salmeterol, concentration-dependent inhibition of release was found for Ag- and anti-IgE-mediated BHR. The Imax of anti-IgE-mediated BHR reached 46 +/- 16% at 30 microM salmeterol. IC30 values were 12 microM for Ag- and 8 microM for anti-IgE-induced BHR. Higher concentrations of salmeterol induced BHR in all subjects (n = 24, 100 microM: 28 +/- 5% BHR), overlapping the inhibitory effect on BHR. Kinetic studies using 30 microM salmeterol (n = 10) showed > 30% inhibition with short preincubation periods (< 10 s). Salbutamol, an older, widely used beta 2-adrenoceptor agonist, had no effect on IgE-mediated BHR (n = 8). We conclude that salmeterol significantly inhibits IgE-mediated histamine release from human leukocytes in the micromolar range.

Adrenergic beta-Agonists↗
PubMed1993

[Studies on the basophil histamine releasability in allergic rhinitis].

Observing the basophil releasability of 17 patients with allergic rhinitis and 14 nonatopic subjects stimulated with house dust mite and concanavalin A (ConA), we found that the histamine release was much higher in patients with allergic rhinitis than in normal controls and that no positive correlation was found between the histamine release rate and the serum total IgE. This result suggests that the enhanced basophil releasability might be an important factor in allergic disorders, and might contribute to a means for the differentiation between allergic and non-allergic disorders.

Adult↗
PubMed1994

Stimulation of mitogen-activated protein kinase activity by different secretory stimuli in rat basophilic leukemia cells.

Ag-induced cross-linking of IgE bound to its high affinity receptor (Fc epsilon RI) at the surface of basophils or mast cells triggers a number of biochemical events culminating in the release of several inflammatory mediators. In rat basophilic leukemia (RBL-2H3) cells expressing the G protein-coupled m1 muscarinic receptor, Ag/IgE-induced cross-linking of Fc epsilon RI, calcium ionophore A23187, and carbachol through M1 receptors stimulated tyrosine phosphorylation of several proteins, including two of 42 and 44 kDa. Proteins of identical molecular masses were recognized by anti-MAP-kinase antibodies, and these immunoreactive proteins exhibited in part a slightly increased molecular mass on SDS polyacrylamide gels after incubation of cells with secretory stimuli. All stimuli led to the activation of MAP kinase, which co-purified on Mono Q chromatography with 42- and 44-kDa proteins, which were tyrosine phosphorylated in response to secretory stimuli and reacted with anti-(MAP kinase) antibodies. Finally, 42- and 44-kDa proteins immunoprecipitated by anti-MAP-kinase antibodies and anti-phosphotyrosine antibodies were recognized by anti-phosphotyrosine and anti-MAP-kinase antibodies, respectively. Primarily threonine and tyrosine residues were found to be phosphorylated in 42- and 44-kDa proteins immunoprecipitated from [32P]phosphate-labeled cells that had been treated with secretory stimuli. The dose dependence of secretagogue-induced MAP kinase activation correlated with that of increases in serotonin release from activated cells, and the maximum of MAP kinase activation coincided with the maximum rate of secretion. Down-regulation or inhibition of protein kinase C as well as incubation of cells with the tyrosine kinase inhibitor genistein markedly inhibited MAP kinase activation in parallel with serotonin release. Taken together, these findings demonstrate that 42- and 44-kDa MAP kinases are activated in response to secretory stimuli and provide some evidence for a functional link between MAP kinase activation and signaling events leading to mediator release in RBL cells.

Animals↗
PubMed1976

[Intracellular histamine content in human basophils and individual variation in allergic persons during densensitization].

A positive correlation has been found to exist between the percentage of basophiles and the histamine content in a suspension of washed human leukocytes obtained from allergic and healthy donors. The mean value of histamine per basophile was 1,9 +/- 0,3 pg. The leukocyte histamine content was measured as a function of time in a non-allergic person and during the desensitization period of allergic patients.

Basophils↗
PubMed1993

[Diagnostic and predictive importance of the blast transformation test and basophil activation test in retinal vasculitis].

22 patients suffering from Birdshot retinochoroidopathy (10), idiopathic vasculitis (6) and Behcet disease (6) and treated by cyclosporine were tested at regular intervals during 11 to 38 months by the lymphocyte stimulation test (LST) and basophil degranulation test (HBDT) with S retinal antigen. These two tests were found frequently positive especially during acute inflammation for the LST. However HBDT was positive in all the patients before relapse of acute inflammation which is in favor of its predictive value and its involvement in the triggering of inflammation at the basophiles or at the local mast cell level.

Basophil Degranulation Test↗
PubMed1993

The interleukin-8-related chemotactic cytokines GRO alpha, GRO beta, and GRO gamma activate human neutrophil and basophil leukocytes.

GRO alpha, a protein structurally related to interleukin-8 (IL-8) and originally described as a melanoma growth stimulatory factor, possesses potent neutrophil-stimulating activity. Recently, two closely related genes, gro beta and gro gamma, were identified. In the present work, the three GRO proteins were chemically synthesized, and their biological activities on human neutrophils and other leukocytes were compared. GRO alpha, GRO beta, and GRO gamma, like IL-8, induced chemotaxis, shape change, a rise in intracellular free calcium levels, exocytosis, and the respiratory burst in neutrophils. The GRO proteins were also active toward basophils as shown by chemotaxis and intracellular calcium concentration changes. The order of potency in neutrophils and basophils was IL-8 > GRO alpha > or = GRO gamma > GRO beta. Of the two IL-8 receptors expressed on human neutrophils, one binds GRO alpha with high and the other with low affinity. Competition binding experiments using radiolabeled IL-8 and GRO alpha revealed the same characteristics for GRO beta and GRO gamma. Similarly, cross-desensitization, as assessed by the stimulus-dependent changes in intracellular calcium concentration, indicated that all three GRO proteins interact with common receptors. From these results, it can be concluded that GRO alpha, GRO beta, and GRO gamma have the same pattern of activity toward human granulocytes and that the differences in amino acid sequence among these proteins have only minor effects on biological activity.

Amino Acid Sequence↗
PubMedDate not supplied

Adult-onset motor neuron disease with basophilic intraneuronal inclusion bodies.

A 53-year-old man initially displayed muscle atrophy and weakness and a slight degree of pyramidal signs, which became more prominent with time. Later, gaze palsy, autonomic dysfunction, and bedsore developed. The total clinical course was 63 months. Pathologically, there was loss of upper and lower motor neurons and other regions, as well as degeneration of the anterior and lateral funiculi of the spinal cord. Round or irregularly-shaped basophilic inclusions were found not only in the motor neurons, but also in other regions such as the putamen, globus pallidus, thalamus, subthalamic nucleus, red nucleus, midbrain tegmentum, pontine nucleus, dentate nucleus, inferior olivary nucleus and others. The inclusions consisted of randomly arranged 12-25 nm thick filaments studded with granules. This patient with adult onset of the disease exhibited features resembling those of "juvenile amyotrophic lateral sclerosis" with basophilic inclusions. Clinically as well as pathologically, the disease manifestations involved many systems other than the motor neurons.

Age Factors↗
PubMed1995

[Nasal smear cytology in bronchial asthma: correlation of appearance and numbers of nasal smear mast cells, eosinophils or basophils and serum IgE antibodies to house dust mite in patients with bronchial asthma].

Nasal smear cytology was studied in pediatric patients with bronchial asthma with special reference with IgE RAST to house dust mite, Dermatophagoides pteronyssinus (Dp). Results obtained were as follows: (1) Numbers of eosinophils on the nasal smear correlated well with Dp RAST score, (2) mast cells were detected before Dp RAST becoming positive and appearance of eosinophils, (3) basophils appeared after detection of eosinophils and only in patients with nasal smear eosinophils. These results suggest that mast cells are the early marker for allergic inflammation and basophils and eosinophils appear in association with overt sensitization with house dust mite in house dust mite-sensitized asthmatic patients.

Adolescent↗
PubMed1996

Basophil-bound IgE and serum IgE directed against Haemophilus influenzae and Streptococcus pneumoniae in patients with chronic bronchitis during acute exacerbations.

The investigation includes 12 patients hospitalized with acute exacerbations of chronic bronchitis (CB) and infected in the lower respiratory tract with Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP). Eight patients were infected the HI, three with SP, and one patient with both species. Basophil-bound IgE and serum IgE directed against these species were examined using the patients' own bacterial isolates. All patients showed IgE-mediated histamine release when their peripheral leukocytes were incubated in vitro with the infecting species, indicating basophil-bound IgE directed against their own bacterium. No IgE-mediated response was obtained in the control group of 12 healthy individuals. Bacteria-specific IgE in serum was demonstrated by immunofluorescence assay and further verified by passive sensitization. There was a positive serum titre in seven of nine patients housing HI and in all SP-infected patients but not in the control group. No synchronism was found between a positive response in the histamine release test and the immunofluorescence assay by parallel testing during the test period. This may be due to a time delay between production of serum IgE and its fixation to the cell surface. The results indicate a potential for a bacteria-specific IgE-mediated immune response in CB. Thus, by triggering mediator release, bacteria may be involved in the pathogenesis of exacerbations in CB.

Aged↗