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  • 1
    Electronic Resource
    Electronic Resource
    Variable expression of activation-linked surface antigens on human mast cells in health and disease (2001)
    Copenhagen : Munksgaard International Publishers
    Immunological reviews 179 (2001), S. 0 
    Details
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Mast cells (MC) are multipotent effector cells of the immune system. They contain an array of biologically active mediator substances in their granules. MC also express a number of functionally important cell surface antigens, including stem cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcεRI), or C5aR (CD88). Respective ligands can induce or promote degranulation, migration, or cytokine production. Other integral surface molecules can mediate adhesion or cell aggregation. Recent data suggest that a number of critical molecules are variably expressed on the surface of human MC. In fact, depending on the environment (organ), stage of cell maturation, type of disease, and other factors, MC express variable amounts of activation-linked antigens (CD25, CD63, CD69, CD88), cell recognition molecules (CD2, CD11, CD18, CD50, CD54), or cytokine receptors. At present, however, little is known about the mechanisms and regulation of expression of such antigens. The present article gives an overview of MC phenotypes in health and disease, and attempts to provide explanations for the phenotypic variability of MC.This study was supported by Fonds zur Förderung der Wissenschaftlichen Forschung in Österreich – FWF grants # P12517 and # P14031, Fondo de Investigaciones Sanitarias de la Seguridad Social (FIS 98/1345), and Fundación Oftalmológica J. Cortés.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-065X.2001.790108.x
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  • 2
    Electronic Resource
    Electronic Resource
    Characterization of recombinant cat albumin (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Indoor allergens derived from animals and mites often contribute to exacerbation of skin manifestations in atopic dermatitis (AD) patients.Objective  To produce and characterize recombinant cat albumin, a cross-reactive animal allergen.Methods  A complete cDNA coding for cat albumin was obtained by RT-PCR amplification from cat liver RNA. Recombinant cat albumin was expressed in Escherichia coli as hexahistidine-tagged protein, purified by nickel affinity chromatography and studied for IgE reactivity with sera from cat-allergic patients by ELISA and immunoblotting. Furthermore, CD203c expression of basophils from cat-allergic patients upon exposure to recombinant cat albumin was analysed.Results  Recombinant cat albumin, a cross-reactive animal allergen sharing most IgE epitopes with its natural counterpart, was produced in E. coli. It was recognized preferentially by IgE from AD patients and elicited IgE-dependent basophil activation in sensitized patients.Conclusions  Recombinant cat albumin may be used as a paradigmatic tool to analyse mechanisms of allergen-triggered exacerbation of AD, for diagnostic and, perhaps for therapeutic purposes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2003.01817.x
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  • 3
    Electronic Resource
    Electronic Resource
    Molecular and immunological characterization of a novel timothy grass (Phleum pratense) pollen allergen, Phl p 11 (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergy to grass pollen is typically associated with serum IgE antibodies to group 1 and/or group 5 allergens, and additionally often to one or several less prominent allergens. Most of the grass pollen allergens identified to date have been characterized in detail by molecular, biochemical and immunological methods, timothy grass being one of the most thoroughly studied species. However, a 20-kDa allergen frequently recognized by IgE antibodies from grass pollen allergics has so far escaped cloning and molecular characterization.Objective To clone and characterize the 20 kDa timothy grass pollen allergen Phl p 11.Methods Phl p 11 cDNA was cloned by PCR techniques, utilizing N-terminal amino acid sequence obtained from the natural allergen. Phl p 11 was expressed as a soluble fusion protein in Escherichia coli, purified to homogeneity and used for serological analysis and to study Phl p 11 specific induction of histamine release from basophils and skin reactivity in sensitized and control subjects.Results Phl p 11 cDNA defined an acidic polypeptide of 15.8 kDa with homology to pollen proteins from a variety of plant species and to soybean trypsin inhibitor. The sequence contained one potential site for N-linked glycosylation. Serological analysis revealed that recombinant Phl p 11 shared epitopes for human IgE antibodies with the natural protein and bound serum IgE from 32% of grass pollen-sensitized subjects (n = 184). Purified recombinant Phl p 11 elicited skin reactions and dose-dependent histamine release from basophils of sensitized subjects, but not in non-allergic controls.Conclusion As the first representative of group 11 grass pollen allergens, Phl p 11 has been cloned and produced as a recombinant protein showing allergenic activity. One-third of grass pollen-sensitized subjects showed specific IgE reactivity to recombinant Phl p 11, corresponding in magnitude to a significant proportion of specific IgE to grass pollen extract.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2002.01467.x
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  • 4
    Electronic Resource
    Electronic Resource
    Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food.Objective Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines.Methods According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25–32 preferably solvent-exposed amino acids were synthesized.Results Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation.Conclusion Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.02081.x
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  • 5
    Electronic Resource
    Electronic Resource
    Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergen-specific immunotherapy represents a causal form of treatment for IgE-mediated allergies. The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies.Objective We analysed allergen-specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1-inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5).Results The strong induction of allergen-specific IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG2 responses were also noted in several actively treated patients. An inhibition of allergen-dependent basophil histamine release was only obtained with sera containing therapy-induced allergen-specific IgG, but not with sera obtained before therapy or from placebo-treated patients. Moreover, patients with therapy-induced allergen-specific IgG antibodies showed a reduced induction of allergen-specific IgE responses during seasonal grass pollen exposure.Conclusion Successful immunotherapy with the MPL-adjuvanted grass pollen allergy vaccine is associated with the production of allergen-specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate-type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2003.01699.x
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  • 6
    Electronic Resource
    Electronic Resource
    Detection of differentiation- and activation-linked cell surface antigens on cultured mast cell progenitors (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Mast cells (MC) are multifunctional effector cells of the immune system. They derive from uncommitted CD34+ hemopoietic progenitor cells (HPC). Depending on the stage of maturation and the environment, MC variably express differentiation- and activation-linked antigens. Little is known, however, about the regulation of expression of such antigens in immature human MC.Methods:  We analyzed expression of CD antigens on human MC grown from cord blood-derived CD34+ HPC. The HPC were isolated by magnetic cell sorting (MACS) and FACS to 〉97% purity, and were cultured in stem cell factor (SCF) and interleukin (IL)-6 with or without additional cytokines (IL-4 or IL-10) in serum-free medium. The cell surface phenotype of MC was determined by monoclonal antibodies and flow cytometry.Results:  Cultured MC progenitors were found to react with antibodies against various CD antigens including CD58, CD63, CD117, CD147, CD151, CD203c, and CD172a, independent of the growth factors used and time-point investigated (days 14–42). CD116 [granulocyte–macrophage colony-stimulating factor receptor α (GM-CSFRα)] and CD123 (IL-3Rα) were expressed on MC precursors on day 14, but disappeared thereafter. Cultured MC did not express CD2, CD3, CD5, CD10, CD19, or CD25. Addition of IL-10 to MC cultures showed no effect on expression of CD antigens. However, IL-4 was found to promote expression of CD35 and CD88 on cultured MC without changing expression of other CD antigens.Conclusions:  Most MC antigens may already be expressed at an early stage of mastopoiesis. Whereas IL-3R and GM-CSFRs are lost during differentiation of MC, these cells may acquire complement receptors (CD35, CD88) under the influence of distinct cytokines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00865.x
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  • 7
    Electronic Resource
    Electronic Resource
    The surface membrane antigen phenotype of human blood basophils (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 49 (1994), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Basophils are effector cells of allergic reactions and express a unique profile of cellular antigens (Ag). Using a combined toluidine-blue/immunofluorescence staining method, we were able to study the cell membrane Ag phenotype of normal human blood basophils with monoclonal antibodies (mAbs) against established and novel CD antigens. According to previous findings, basophils express CD9 (p24), CDlla (LFA-1 alpha-chain), CDllb (C3biR), CDllc (CR4), CD13 (aminopeptidase N), CDwl7 (lactosylceramide), CD18 (beta-chain of β2), CD25 (IL-2R alpha-chain), CD26 (dipeptidylpeptidase), CD31 (PECAM), CD35 (CR1), CD38 (T10), CD43 (leukosialin), CD44 (Pgp-1), CD45 (pan-leukocyte Ag), and CD63 (basophil activation Ag). Various novel CD Ags were detected on basophils, including membrane cofactor protein (MCP) (CD46), the N-linked glycan CD47, decay-accelerating factor (DAF) (CD55), membrane attack complex inhibitory factor (MACIF) (CD59), LFA-3 (CD58), ICAM-2 (CD 102), ICAM-3 (CD50), C5a receptor (CD88), MIC-2/E2 (CD99), and the interleukin-1 (IL-1) R type II (CD121b). These data provide further evidence that basophils express a unique profile of surface membrane receptors for cytokines and immunomodulating compounds, as well as adhesion molecules and surface glycolipids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1994.tb00788.x
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  • 8
    Electronic Resource
    Electronic Resource
    Differential response of human basophils and mast cells to recombinant chemokines (1995)
    Springer
    Annals of hematology 70 (1995), S. 251-258 
    Details
    ISSN: 1432-0584
    Keywords: Key words Human basophils ; Mast cells ; Recombinant chemokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1α, MIP-1β, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1α, MIP-1β, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 μg/ml: 26.9±3.4%; other chemokines: 〈5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (〈1 μg/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n=2), skin (n=1), uterus (n=3), or tonsils (n=3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2Rβ, CD63, IL-3Rα, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01784044
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of interferon-α2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis (2000)
    Springer
    Annals of hematology 79 (2000), S. 660-666 
    Details
    ISSN: 1432-0584
    Keywords: Keywords Mastocytosis ; Progenitor cells ; Interferon-α ; Tryptase ; Histamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interferon (IFN)-α, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-α effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-α2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to 〉1400 ng/ml). PBMNCs were collected before and during IFN-α2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-α2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-α2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-α2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-α2b. In summary, our data show that IFN-α2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-α treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770000206
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  • 10
    Electronic Resource
    Electronic Resource
    Differential response of human basophils and mast cells to recombinant chemokines (1995)
    Springer
    Annals of hematology 70 (1995), S. 251-258 
    Details
    ISSN: 1432-0584
    Keywords: Human basophils ; Mast cells ; Recombinant chemokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1α, MIP-1β, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MlP-la, MIP-1β, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 μg/ml: 26.9 ± 3.4%; other chemokines: 〈 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (〈 1 μg/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n=2), skin (n=1), uterus (n=3), or tonsils (n=3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2Rβ, CD63, IL-3Rα, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01784044
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