Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BASOPHILS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1996

Histamine releasability of basophils and skin mast cells in chronic urticaria.

In order to clarify the pathogenetic role of basophils and mast cells in chronic urticaria, histamine and leukotriene (LT)C4 release was examined in washed mixed leukocytes (n = 8) and skin mast cells (n = 5) from patients with chronic urticaria and compared with the same cells from normal controls (n = 9). Anti-IgE-stimulated basophil histamine release was significantly reduced in urticaria patients (median 2.9% vs 15.1% in normal controls), whereas histamine release to A23187, FMLP, and PAF, as well as anti-IgE-induced LTC4 release, showed no differences in both groups. In contrast, anti-IgE-stimulated skin mast cells from urticaria patients reacted similarly to those of controls (median histamine release 11.4% vs 14.2% in normal controls). Pretreatment of the cells with interleukin (IL)-3 upregulated responsiveness of basophil histamine release to anti-IgE in urticaria patients (median histamine release 14.3%), but pretreatment with the H2-antagonist cimetidine showed no effect. These data show that reduced basophil histamine releasability in chronic urticaria is not H2 mediated. It is a stimulus-, mediator-, and cell type-restricted phenomenon that can, at least partially, be reversed in the presence of the cytokine IL-3.

Adult↗
PubMed1996

Enhancement of basophil histamine release by interleukin-3: reduced effect in atopic subjects.

The inducing and enhancing effects of interleukin-3 (IL-3) on basophil histamine release in patients with respiratory allergy (n = 28) and in normal subjects (n = 22) were compared. Leukocyte suspensions, prepared by dextran sedimentation, were stimulated with anti-IgE (1/5000), N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM), and IL-3 (0.1-10 ng/ml), and histamine concentration was measured by an automated fluorometric method. A trend toward higher histamine release after challenge with anti-IgE, FMLP, and IL-3 was found in atopic subjects. Preincubation of basophils with IL-3 resulted in a dose-dependent increase of anti-IgE- and FMLP-induced histamine release, with a more marked effect in nonatopic than in atopic subjects. Mean net enhancement of anti-IgE-induced histamine release by 10 ng/ml IL-3 was 2.5 +/- 5% in atopic subjects and 29.6 +/- 4.2% in nonatopic subjects (P < 0.001). The enhancement of FMLP-induced histamine release by IL-3 was 10.3 +/- 3.9% in atopic patients and 29 +/- 2.4% in nonatopic subjects (P < 0.01). In atopic subjects, a negative correlation was found between anti-IgE- or FMLP-induced histamine release and net enhancement by IL-3 (r = -0.45, P < 0.02; r = -0.48, P < 0.01, respectively). The results of this study indicate that in atopic subjects IgE-mediated histamine release can scarcely be enhanced by a basophil response modifier such as IL-3. It is conceivable that the frequent basophil stimulation in atopic patients leads to a reduced sensitivity to the enhancing effect of IL-3.

Adult↗
PubMed1998

The in vivo effect of isocyanate-induced asthma on basophil histamine release.

In vitro studies have suggested that basophils are involved in the asthmatic response to isocyanate. Classified by the type of airway response, three groups of patients exposed to isocyanate were studied: 1) nonreactive (n=3), 2) immediate responders (n=4), and 3) late responders (n=4). Basophil histamine release to concanavalin A (conA), FMLP, and anti-IgE was evaluated before and during the airway response. Histamine release significantly (P=0.009 for conA and 0.03 for anti-IgE) increased after exposure to isocyanate only in the group which had late bronchial response. Additionally, good correlation was found between baseline FEV1/FVC% and degree of histamine release of basophils stimulated with conA. These findings support a role for basophils in the late asthmatic response to isocyanate.

Adult↗
PubMed2006

Basophil allergen threshold sensitivity: a useful approach to anti-IgE treatment efficacy evaluation.

BACKGROUND: Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment. METHODS: Basophils from timothy grass pollen allergic patients were, by flow cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring CD63 up-regulation on CD203c-identified basophils. The results were compared with maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick test end-point allergen titration, (SPT-sens), nasal provocation titration tests (nasal provocation titre) and serum IgE and IgE antibody concentrations. RESULTS: There was a significant correlation (r = 0.50, P = 0.01) between CD-sens and SPT-sens, CD-sens and the IgE antibody concentration in percentage of 'total IgE' (relative IgE antibody concentration) (r = 0.72, P < 0.001) as well as between CD-sens and nasal provocation titre (r = 0.54, P < 0.05) but, in contrast, CD-max did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal provocation titre, absolute and relative IgE antibody concentration or CD-sens. CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD-max, four of seven symptom-free patients on omalizumab would have been classified as having ongoing allergy. CONCLUSIONS: CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information.

Allergens↗
PubMed2006

Serum-induced basophil CD63 expression by means of a tricolour flow cytometric method for the in vitro diagnosis of chronic urticaria.

BACKGROUND: Functional autoantibodies against the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) identify a subset of patients with chronic urticaria (CU) due to autoreactivity, as assessed by an in vivo positive response to autologous serum skin test (ASST). We performed a study to standardize the serum-induced basophil activation assay by flow cytometry (FCM) using a new tricolour method, assessing the diagnostic performance of this test in discriminating between ASST+ and ASST- CU patients. METHODS: Sera of 64 CU patients (22 ASST+ CU and 42 ASST- CU) and 10 healthy subjects were tested for their ability to induce basophil CD63 expression when incubated with whole blood of both atopic (DA) and non-atopic donors (DNA). Using a triple-labelled strategy with anti-CD123, anti-HLA-DR and anti-CD63 antibodies, CD63+ basophils were identified on a selected population of CD123+ HLA-DR- cells. In 3 ASST+ CU patients who underwent cyclosporine therapy, the assay was performed before and after treatment. RESULTS: The ASST+ CU sera resulted in a significant higher induction of basophil CD63 expression compared with ASST- CU and healthy donors sera; when whole blood from DA was used, sensitivity and specificity of the assay were 95.5% and 90.5% respectively. ASST+ CU serum activity was significantly decreased during cyclosporine A treatment, in parallel with clinical remission. CONCLUSIONS: Chronic urticaria serum-induced CD63 expression assay performed on DA whole blood by means of our tricolour FCM method could be the most useful tool for identification of a subset of patients with autoimmune CU and may become a promising tool also for monitoring treatment efficacy.

Adult↗
PubMed2006

Simultaneous exposure of several allergens has an additive effect on multisensitized basophils.

BACKGROUND: Patients immunoglobulin (Ig)E-sensitized to more than one allergen in their environment often have more symptoms than mono-sensitized individuals, which indicates that the allergens may have an additive effect. In order to study if such an effect could be detected on the inflammatory, cellular level, multisensitized basophils were challenged with various dose combinations of two relevant allergens. METHODS: Basophils from patients IgE-sensitized to timothy/cat, birch/cat, timothy/mite and cat/mite were challenged with serial dilutions of different combinations of the two allergens. The basophil response was measured as CD63 expression analysed by flow cytometry. RESULTS: The doses of each allergen in the pair had an additive effect resulting in a shift of the dose-response curve to higher CD63 percentages and higher CD-sens. CONCLUSIONS: If a patient has IgE antibodies and thus sensitized basophils to more than one allergen, to which he is simultaneously exposed, the additive effect should be considered. Even low concentrations of IgE antibodies could be of clinical relevance in such a situation.

Allergens↗
PubMed1992

Regulation of human basophil activation. IV. Dissociation between cationic dye binding and histamine release: role of Ca2+ ions.

In previous studies we observed that in vitro histamine release from human basophils could be dissociated from the loss of affinity of basophil granules for a cationic dye, toluidine blue. In the present study we further explored the intracellular signals leading to the decrease in toluidine blue positive basophil (TB+) numbers, with or without histamine release. Since Ca2+ mobilization is a crucial event in secretion and particularly in histamine release, we studied the role of Ca2+ in histamine release as compared to TB+ decrease. In the presence of external Ca2+ (2 mM): i) Ca2+ channel antagonists verapamil and nifedipine up to 10 microM were without effect on IgE-mediated histamine release and TB+ decrease; ii) loading of the leucocytes with Quin2 or preincubation with TMP-8, an internal Ca2+ antagonist, significantly inhibited the release of histamine and the decrease of TB+ basophils. In the absence of added external Ca2+:i) histamine release was abolished whereas the decrease of TB+ was not modified, even in the presence of EGTA;ii) the decrease of TB+ could be inhibited by prolonged EGTA preincubation, by Quin2 loading and incubation with TMB-8. We conclude that histamine release requires both external Ca2+ influx and mobilization of internal Ca2+. In contrast, no influx of external Ca2+ is required for TB+ decrease in which, however, internal Ca2+ mobilization appears to play an important role.

Antibodies, Anti-Idiotypic↗
PubMed1983

Adenosine inhibits and potentiates IgE-dependent histamine release from human basophils by an A2-receptor mediated mechanism.

Adenosine added to human basophils before anti-IgE challenge inhibited histamine release, whereas addition after challenge potentiated release. Peak responses for the two effects occurred 15 min before and after challenge respectively. The effects of adenosine on histamine secretion were dose-related over concentration ranges of 1-100 microM for inhibition and 0.01-1 microM for potentiation. The capacity of adenosine to inhibit and potentiate histamine secretion was inversely related to the strength of immunological challenge. The ability of theophylline (50 microM) to inhibit and dipyridamole (1 microM) to enhance slightly adenosine-induced responses, and the differing pharmacological effect of 2',5'-dideoxyadenosine suggested that adenosine's effects on basophil histamine secretion were mediated by stimulation of cell surface adenosine receptors. The order of potency of adenosine and its analogues L- and D- N6-phenylisopropyladenosine (PIA) and 5'-N-ethylcarboxamideadenosine (NECA) in inhibiting and potentiating IgE-dependent histamine release from basophils indicated that both responses were mediated by stimulation of the adenosine A2-receptor subtype. The capacity of adenosine to cause a transient increase of cyclic AMP levels in 40-70% basophil-enriched leucocytes confirmed the association between stimulation of A2-receptors and activation of adenylate cyclase.

Adenosine↗
PubMed1997

Ultrastructural localization of Charcot-Leyden crystal protein in human eosinophils and basophils.

The Charcot-Leyden crystal (CLC) protein with lysophospholipase activity and carbohydrate-binding properties is a characteristic constituent of eosinophils and basophils. We investigated its subcellular distribution using immunoelectron microscopy. Eosinophil progenitors, mature eosinophils and basophils all contained CLC protein in their cytosol and in the euchromatin of the nucleus. A minor population of granules in eosinophils, increasing in number with maturation, and a more abundant granule-population in basophils, were found to contain CLC protein. Double-labeling experiments showed, in eosinophils, that CLC protein-containing granules contain also eosinophil peroxidase, a characteristic specific granule protein. This suggests a relationship between the CLC protein-containing organelle and the specific granule. In basophils both the CLC protein positive and the negative granules showed the same characteristic particulate-like structure of the granular matrix and both share the same membrane marker CD63. In nasal polyps, macrophages were observed phagocytosing necrotic eosinophils. In these macrophages CLC protein-containing vesicles were observed, probably representing late endosomes. The dual (cytosolic/nuclear and granular) localization of CLC protein suggests that this protein enters both a secretory and a nonsecretory pathway during its biosynthesis, indicating functional roles for this protein both within the cell and extracellularly.

Basophils↗
PubMed1980

Cutaneous basophil hypersensitivity and contact sensitivity after cutaneous Trichophyton mentagrophytes infection.

The histopathology of cutaneous lesions and trichophytin skin test responses was examined by light microscopy after the infection of strain 2 guinea pigs with Trichophyton mentagrophytes. Skin biopsies were fixed and stained with procedures which allowed differentiation of the polymorphonuclear granulocytic leukocytes that were present in lesions or skin test reactions. Basophils comprised about one-third of the leukocytes infiltrating the 24 to 48-h trichophytin skin test reactions of guinea pigs sensitized by a cutaneous T. mentagrophytes infection. These results were comparable to the percentage of basophils counted in skin test lesions elicited by the contact agent dinitrochlorobenzene and are consistent with previously published descriptions of cutaneous basophil hypersensitivity. In contrast, the active T. mentagrophytes lesion in the skin of guinea pigs sacrificed at defined intervals after infection or reinfection did not appear to contain similarly elevated numbers of basophils. The early inflammation in primary T. mentagrophytes-induced skin lesions can be characterized histologically as a primary irritant dermatitis which evolves, during the course of the disease, into a chronic mononuclear inflammation. This shift apparently results from host sensitization to fungal antigens during infection and the concurrent development of acquired immunity. Reinfection of guinea pigs with T. mentagrophytes resulted in an accelerated cutaneous inflammation that was temporally and histologically similar to allergic contact dermatitis. These results support the hypothesis that contact sensitivity to T. mentagrophytes develops during the primary cutaneous infection of guinea pigs and is an early component of the hypersensitivity response to reinfection.

Animals↗
PubMed1989

Avian erythroblastosis virus transforms a novel mast cell-basophil precursor target in the Japanese quail.

Hematopoietic cells of the Japanese quail were transformed by avian erythroblastosis virus in vivo and in vitro. In both circumstances, the infected hematopoietic tissues exhibited a dual oncogenic response of erythroid and mast cell-basophil elements. The erythroid transformants escaped the avian erythroblastosis virus block in differentiation and progressed to hemoglobinization. Resulting basophilic cells were morphologically, biochemically, and ultrastructurally identical to mast cell-basophils observed in other species. None of the virally transformed cells actively produced reverse transcriptase activity. Nonproducer cell lines synthesized viral RNA and both v-erbA and v-erbB proteins. These results indicate that the Japanese quail has a viral target cell different from that of the chicken. The implications of a single bipotential transformation target yielding both erythroid and mast cell-basophil colonies is discussed.

Alpharetrovirus↗
PubMed1982

Basophil degranulation induced by cigarette smoking in man.

There is some evidence that histamine could be a mediator of the immediate broncho-constriction that follows cigarette smoking. Since the chief reservoir of histamine in normal human blood is the basophil, we studied the acute effects of cigarette smoking on these cells. Capillary blood samples were obtained from 27 healthy young male smokers, before and 10 minutes after smoking. Basophils were collected and concentrated from these samples by a millipore membrane filter technique, stained with toluidine blue, and classified according to the staining characteristics and location of their cytoplasmic granules. This classification differentiated the "intact" from the "degranulated" basophils. A significant increase in degranulated cells and decrease in intact cells (p less than 0.001) was observed after smoking. Since histamine is present in the basophil granules, these findings suggest that cigarette smoking causes histamine release.

Adult↗
PubMed1983

Plasma histamine in asthmatic and control subjects following exercise: influence of circulating basophils and different assay techniques.

Arterial plasma histamine concentrations were measured after exercise in 10 subjects with extrinsic atopic asthma, 10 who were non-atopic and non-asthmatic and seven who were atopic but non-asthmatic, by a single isotope radioenzymatic assay. Significantly higher plasma histamine concentrations were found in the asthmatic subjects before exercise than in the non-atopic controls (p less than 0.05). The mean histamine concentration rose after exercise in all groups but the increased levels were not significantly different from pre-exercise values. Similarly, mean circulating basophil counts increased in all groups after exercise, and a highly significant correlation was found between basophil counts and whole blood histamine concentrations (p less than 0.001). In vitro studies showed that there was a significant correlation between the number of basophils added to plasma samples and the concentrations of histamine subsequently detected. Although the mean concentrations of plasma histamine and whole blood histamine and number of basophils in the atopic control group were intermediate between those found in the atopic asthmatic and non-atopic controls, none of the differences was significant. Venous plasma histamine concentrations after exercise were measured in a further five subjects with extrinsic atopic asthma and five non-atopic, non-asthmatic subjects before and after exercise with the more sensitive and specific double isotope radioenzymatic assay. Concentrations of plasma histamine measured by this assay were about one tenth of those measured by the single isotope radioenzymatic assay. Although a small rise in mean plasma histamine concentration occurred in both groups after exercise there was no significant difference in these levels either between or within the groups. We find no evidence from these studies on measurement of peripheral blood histamine to support the hypothesis that mast cell mediator release is implicated in the pathogenesis of exercise induced asthma.

Adult↗
PubMed2005

Characterization of modified allergen extracts by in vitro beta-hexosaminidase release from rat basophils.

BACKGROUND: To date, there is no well-established test available that can be used to measure functional properties of modified allergens (allergoids). Due to the cross-linking process, the IgE-binding capacity of the allergens, normally necessary for their characterization, is lost. The aim of this study was to test whether the rat basophilic leukaemia (RBL) cell assay (beta-hexosaminidase release by rat basophils upon allergen stimulation) can be adopted to characterize allergoids and to evaluate the assay for testing allergoids and native allergens as well. METHODS: Mice were immunized with native and modified Phleumpratense extracts in the presence of alum. Their sera were used to sensitize RBL-2H3 cells and measure basophil stimulation induced by different allergen extracts in the presence or absence of various additives. RESULTS: Sera containing specific IgE against both extract formulations were obtained. Native as well as modified extracts induced dose-dependent beta-hexosaminidase release from RBL cells. Both extracts were used to evaluate the characteristics of the assay, which showed high precision. Storage conditions were chosen to enhance extract degradation, which could be read directly from the altered stimulatory capacity of the extracts. Additives turned out to have diverse effects on the assay, whereas phenol had no measurable effect, alum had an inhibitory effect and glycerol elevated basophil activation. CONCLUSIONS: For the first time, a reliable, precise in vitro assay is available that is able to directly measure the properties of modified allergen extracts after their production process. The test is well evaluated and its advantages and limitations are discussed in this report.

Allergoids↗
PubMed2005

Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels.

BACKGROUND: The high-affinity IgE receptor, FcepsilonRI, is unresponsive on mast cells and basophils from people in several populations through an unknown mechanism. Similarly, FcepsilonRI-positive basophils from 'nonreleasers' are IgE-unresponsive and are deficient in the tyrosine kinase Syk. OBJECTIVE: To test the hypothesis that cross-linking FcepsilonRI on mast cells and basophils leads to FcepsilonRI nonresponsiveness through reduction in Syk protein levels. METHODS: Human mast cells and basophils were used to determine if FcepsilonRI hyporesponsiveness correlated with reduced Syk levels. RESULTS: It is shown that suboptimal antigen challenge, that did not lead to significant mediator release, induced nonresponsiveness and correlated with reduced Syk. Other IgE-associated signaling molecules were unaffected by the same treatment. The ability of IgE-unresponsive mast cells to regain FcepsilonRI responsiveness is paralleled by increased cellular Syk levels in vitro. The reduction of Syk levels with suboptimal antigen concentrations was calcium independent and mediated through a proteasome-dependent mechanism. CONCLUSION: These findings confirm and extend our knowledge about a novel regulatory mechanism for maintaining FcepsilonRI in a quiescent state. This mechanism may also explain why low concentrations of allergen given to patients during allergen immunotherapy induce FcepsilonRI nonresponsiveness and therapeutic benefit without inducing systemic anaphylaxis.

Basophils↗
PubMed1986

The pharmacologic control of mediator release from human basophils and mast cells.

Insight into the pathogenesis of human allergic and inflammatory disorders has been obtained through a combination of in vitro and in vivo studies. These investigations have demonstrated that human basophils and mast cells release mediators after nonimmunologic as well as immunologic activation in vitro and in vivo: nonimmunologic triggers include changes in osmolarity. Although these cells share many properties, including the presence of high-affinity receptors for IgE on their cell surface, the presence of histamine in granules, the ability to generate and release large quantities of leukotriene C4 (LTC4) after activation, and the ability of several pharmacologic agents including phospholipase inhibitors, acetylene analogues of arachidonic acid (ETYA, ETI), methylxanthines, prostaglandin E2 (PGE2) beta-agonists, and cyclic AMP to inhibit mediator release, they also display notable differences. Human lung mast cells generate and release large quantities of prostaglandin D2 (PGD2) after activation; basophils generate no known cyclooxygenase product. Indomethacin, arachidonic acid, and 5-hydroperoxyeicosatetraenoic acid (5-HPETE) all enhance histamine and LTC4 release from human basophils; no effect is seen with human lung mast cells. Overnight incubation of basophils with glucocorticoids produces a marked inhibition of mediator release; this treatment does not affect the release of mast cell mediators. These in vitro observations are consistent with our in vivo observations and our hypotheses concerning the importance of these cells in allergic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1996

Heterogeneity of human skin mast cells and human basophils. I. Pharmacological experiments with activators and inhibitors of protein kinase C.

Skin mast cells and basophilic leukocytes are known as key elements of acute and subacute IgE-mediated immune responses of the skin. The present paper investigated pharmacological aspects of signal transduction pathways of both cell types using activators and inhibitors of protein kinase C (PKC). The nonselective inhibitor K252a suppressed Fc epsilon RI-mediated histamine release from basophils and skin mast cells dose-dependently with IC50 values of 0.01 and 0.28 mumol/l. However, preincubation of both cell populations with kinase inhibitors showing in vitro selectivity for PKC (Ro 31-7549, calphostin C, GF 109203X) revealed a distinct modulation of cell response: IgE-mediated mediator release was inhibited only in skin mast cells, whereas in experiments with basophils a concentration-dependent potentiation of exocytosis was observed. Further evidence for heterogenous biochemical signals following activation of both cell types derived from studies with the phorbol ester TPA. With respect to acute and late-phase IgE-mediated skin reactions, we suggest that distinct signal transduction mechanisms at the level of PKC (isozymes) in basophils and skin mast cells might reflect their functional heterogeneity.

Animals↗
PubMed1977

Failure of the putative IgE pentapeptide to compete with IgE for receptors on basophils and masts cells.

We have examined the claim that a pentapeptide resembling a portion of epsilon-chain of IgE can inhibit allergic reactions by competing with IgE for basophil-mast cell IgE receptors. Four laboratories with expertise in different areas collaborated. The following was found. (1) There was no evidence, by autoradiography, that the pentapeptide could block IgE fixation to basophils or displace IgE from these cells. (2) There was no evidence, by histamine release studies that the pentapeptide could block basophil sensitization or remove IgE from actively sensitized cells. The pentapeptide, also, did not impair antigen-induced histamine release. (3) There was no evidence that the pentapeptide could block the skin test response in Prausnitz-Küstner testing with the antigen injected intradermally or orally administered. Neither the correct pentapeptide sequence from the epsilon-chain nor the Fc" fragment of IgE impaired the P-K test. In each series of experiments, IgE myeloma protein, as a positive control, blocked the allergic response. The failure of the pentapeptide to block these reactions was observed at molar ratios of pentapeptide/IgE of 10(6) to 10(7). Our results, therefore, provide no evidence for competition between the pentapeptide and IgE. Even if there should be some weak affinity between the pentapeptide and IgE receptors on basophils or mast cells this would, by virtue of quantitative considerations, be of no clinical relevance.

Autoradiography↗