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P Valent

Publications and source records attributed to P Valent.

At least 181 records · Page 10Linked to original sources
PubMed1994

The surface membrane antigen phenotype of human blood basophils.

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), CD11a (LFA-1 alpha-chain), CD11b (C3biR), CD11c (CR4), CD13 (aminopeptidase N), CDw17 (lactosylceramide), CD18 (beta-chain of beta 2), 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.

Antigens, Surface↗
PubMed1994

Inhibition of stem cell factor dependent formation of human mast cells by interleukin-3 and interleukin-4.

In murines, interleukins (IL) 3, 4, 9, and 10, nerve growth factor, and stem cell factor induce or promote growth and differentiation of mast cells (MC). Increased stimulation and synergy was observed when combinations of cytokines were used. In man, no growth factor for human MCs had been identified until recently, when SCF was found to induce in vitro growth and differentiation of human MCs. In the present study, the effects of recombinant human IL-3 and IL-4 on SCF-dependent differentiation of human MCs from their circulating progenitor cells in long-term culture were analyzed. Surprisingly, both IL-3 and IL-4 were found to inhibit SCF-dependent formation of human MCs (SCF, 100 ng/ml: 36.4 +/- 18.7 x 10(3)/ml; SCF + IL-3, 100 U/ml: 23.4 +/- 4.2 x 10(3)/ml; SCF + IL-4, 100 U/ml: 7.4 +/- 4.4 x 10(3)/ml) and synthesis of MC tryptase (SCF, 100 ng/ml: 73.2 +/- 17.6 ng/ml; SCF + IL-3, 100 U/ml: 10.8 +/- 3.1 ng/ml [p < 0.01]; SCF + IL-4, 100 U/ml: 8.1 +/- 1.5 ng/ml, [p = 0.02]). The inhibitory effects of these cytokines on SCF-dependent formation of human MCs were associated with an increase in the number of macrophages (IL-3) or lymphocytes (IL-4) in the same cultures and may be due to competitive recruitment of cells from a pool of multilineage hematopoietic progenitor cells.

Cell Differentiation↗
PubMed1993

cDNA cloning of a major allergen from timothy grass (Phleum pratense) pollen; characterization of the recombinant Phl pV allergen.

We isolated a cDNA encoding a major grass pollen allergen from a timothy grass (Phleum pratense) pollen expression cDNA library using allergic patients' IgE. The complete cDNA encoded an allergen that binds IgE from about 80% of grass pollen-allergic patients. Significant sequence homology was found to other major grass pollen allergens from Kentucky bluegrass (Poa pratense) as well as from rye grass (Lolium perenne) which originally were believed to form different identities. Using different monoclonal and polyclonal antibodies raised against group V allergens we identified the recombinant protein as a group V allergen from timothy grass, Phl p V. In IgE-binding studies it is demonstrated that the rPhl p V allergen can be used to block binding of patients' IgE to natural group V isoallergens on two-dimensional immunoblots. IgE inhibition experiments show that up to 60% of grass pollenspecific IgE can be preadsorbed with the rPhl p V allergen from patients sera. The purified rPhl p V induced specific histamine release of blood basophils from grass pollen-allergic patients. This emphasizes the usefulness of the rPhl p V for diagnostic and therapeutic purposes and corroborates the view that specific diagnosis and therapy of type l allergy could be performed with a limited panel of relevant recombinant allergens.

Amino Acid Sequence↗
PubMed1993

Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly-, CD14-, CD17-, colony-forming cell.

Mast cells (MC3) belong to the hemopoietic system and arise from hemopoietic precursor cells. Human MC progenitors can be detected in the bone marrow as well as in the peripheral blood (pb) and are responsive to the mast cell growth factor SCF, the ligand of the c-kit tyrosine kinase receptor. However, little is known about the subsets of cells that become committed to and differentiate into mature human MC. In this study, the identity of the circulating MC progenitor, previously felt to be a monocyte (Mo) or basophil (Ba), was investigated. For this purpose, CD14+ pb monocytes, CD17+ pb basophils and CD34+ cord blood cells were purified to homogeneity (> 95%) from mononuclear cells (normal adult donors, n = 17, cord blood, n = 2) by counter-flow centrifugation followed by cell sorting with mAb. In the presence of rhSCF, MC developed in long term suspension culture from pure CD34+ cells but not from pure Mo, pure Ba, or Ly (MC-tryptase levels on day 42: CD14+ Mo: 3.7 +/- 0.8 vs CD17+ Ba: 3.2 +/- 0.5 vs Ly: 2.0 +/- 1.5 vs control: 196.5 +/- 92.5 ng/ml, p < 0.001). Depletion of CD34+ cells from MNC resulted in a loss of MC in long term suspension culture, whereas depletion of either Mo, Ba, or Ly did not. In methyl-cellulose cultures in the presence of rhSCF, MC and tryptase could be detected in pure (CFU-mast) and mixed (CFU-myeloid/mast) MC colonies. Together, MC do not originate from circulating Mo, Ba, or Ly. The circulating MC progenitor is a CD34+, c-kit+, Ly-, CD14-, CD17- colony-forming cell. This is the first definitive demonstration that mast cells are replenished directly from early hemopoietic progenitors and thus form a unique cell lineage within the hemopoietic system.

Antigens, CD↗
PubMed1993

Purification and characterization of recombinant Bet v I, the major birch pollen allergen. Immunological equivalence to natural Bet v I.

Pollen from trees of the order Fagales (e.g. birch, alder, hazel, oak, and hornbeam) are a major cause of Type I allergies observed in early spring. Previously, we reported the cloning and sequencing of Bet v I, the major birch pollen allergen, which showed high sequence similarities to a family of plant pathogen-activated genes (Breiteneder, H., Pettenburger, K., Bito, A., Valenta, R., Kraft, D., Rumpold, H., Scheiner, O., and Breitenbach, M. (1989) EMBO J. 8, 1935-1938). Here, we present the results on the expression, purification, and characterization of recombinant Bet v I produced in Escherichia coli as fusion and non-fusion protein, respectively. The purified recombinant proteins were analyzed to verify purity and structural integrity, and their immunological properties were compared to those of Bet v I isolated from birch pollen (natural Bet v I). Immunoblot analyses showed that the recombinant proteins are specifically recognized by monoclonal antibodies raised against natural Bet v I as well as by IgE from birch pollen-allergic patients. However, enzyme-linked immunosorbent assays revealed a decreased IgE-binding activity of the recombinant fusion Bet v I compared to the non-fusion and natural Bet v I proteins, which probably results from conformational changes due to the fusion tail. Recombinant non-fusion Bet v I was equivalent to natural Bet v I with respect to IgE-binding properties, the ability to induce in vitro proliferation of allergen-specific T-cell clones, and the ability to release histamine from basophils derived from birch pollen-allergic patients.

Allergens↗
PubMed1993

Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product.

Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently identified stem cell factor, was studied on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10(-9) M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN-gamma, vitamin D3, retinoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.

Base Sequence↗
PubMed1993

Induction of specific histamine release from basophils with purified natural and recombinant birch pollen allergens.

As much as 15% of the population in industrialized countries suffers from type I allergic symptoms (rhinitis, conjunctivitis, and bronchial asthma). One approach toward this disease involves the production of recombinant allergens in Escherichia coli and their purification for diagnostic and therapeutic purposes. In this study we compared the IgE-binding capacity of natural and recombinant birth allergens with their functional ability to release histamine from allergic patients' basophils via cross-linking of high-affinity Fc epsilon-receptors. The recombinant as well as pollen-derived Bet v I and birch profilin (Bet v II) were purified and tested in parallel on IgE immunoblots and in in vitro histamine release tests (n = 21). We observed an excellent correlation between allergen-induced histamine release and birch pollen RAST (r = 0.881, p < 0.002). Nonspecific histamine release as a result of a cell toxic effect of the allergen preparations was never observed from basophils of donors without birch pollen allergy. The specificity of the presented effector model is also documented by the specific desensitization of patients' basophils with the recombinant allergens. These data may provide a basis for the use of purified recombinant allergens in sensitive and specific in vitro allergy tests monitoring the effector situation in allergic patients, which therefore may represent a possible alternative for in vivo diagnostic methods.

Allergens↗
PubMed1993

Specific activation of human mast cells by the ligand for c-kit: comparison between lung, uterus and heart mast cells.

Recent data suggest that stem cell factor (SCF or c-kit ligand, KL) is a major regulator of human mast cells (MCs). In the present study, MCs derived from the lung (n = 8), uterus (n = 14) and heart (n = 4) were analyzed for expression of c-kit receptor and for responses to recombinant SCF. MCs of all organs tested were recognized by mAbs to c-kit (YB5.B8, SR-1) as assessed by combined toluidine blue/immunofluorescence staining. Activation by rhSCF (10 ng/ml, 60 min) resulted in histamine release from lung MCs (SCF 12.8 +/- 2.7% histamine release; control 2.8 +/- 0.8%, p < 0.01), uterus MCs (SCF 16.8 +/- 5.8%; control 5.2 +/- 2.5%, p < 0.01) and heart MCs (SCF 18.4 +/- 2.6%; control 1.7 +/- 0.23%, p < 0.01). Short-term pre-incubation with rhSCF (15 min) did not result in histamine secretion (p > 0.05), but in an increase (lung 2.4 +/- 1.0 fold; uterus 2.1 +/- 1.1 fold, and heart 2.0 +/- 0.4 fold) of alpha IgE-induced mediator release (p < 0.05). The effects of SCF were dose-dependent (maximum responses at 10-100 ng/ml) and dependent on extracellular calcium. A monoclonal antibody to SCF was found to inhibit the effects of SCF on MCs. Furthermore, MCs could be desensitized specifically by pre-incubation of MCs with rhSCF in Ca-free medium. Together, these data suggest that SCF triggers mediator secretion from MCs in various organs via binding to the c-kit receptor.

Antibodies, Monoclonal↗
PubMed1993

[Effector cells in allergy: biological principles and new pharmacologic concepts].

The clinical symptoms of allergy are caused by cellular (IgE-triggered) responses to an allergen. Effector cells of allergy include eosinophil and basophil granulocytes, as well as tissue mast cells. Growth and accumulation, as well as IgE-dependent and independent functions of these cells are regulated by distinct proteohormones and peptides. The hemopoietic cytokines IL-3 (interleukin-3), IL-5 and GM-CSF (granulocyte-macrophage colony-stimulating factor) are involved in the regulation of basophils (and eosinophils), whereas the ligand for c-kit, SCF (stem cell factor) is a mast cell-specific agonist. Basophils and mast cells express high-affinity IgE-binding sites. Allergen binding to IgE on mast cells and basophils, and consecutive cross-linking of IgE receptors is followed by production and/or secretion of inflammatory mediator substances. Specific activation and deactivation of mast cells/basophils in vitro has been demonstrated by use of recombinant cytokines and allergens, and specific haptens or by use of novel drugs, and should lead to epitope-specific diagnosis and better management of allergic diseases in the future.

Allergens↗
PubMed1993

[New concepts in therapy of type I allergic diseases].

The molecular characterization of allergens with recombinant DNA techniques allowed cDNA sequences to be obtained and, hence, information regarding the primary structure of allergens. It is now possible to express well-defined recombinant allergens in heterologous expression systems and to obtain large amounts of highly pure recombinant allergens for the improvement of current diagnosis and therapy of type I allergic diseases. Due to extensive cross-reactivities and structural similarities of the relevant allergens it is possible to define a limited number of allergens, which is a prerequisite for allergen-specific therapeutic concepts. Specific concepts of active immunotherapy and strategies of passive therapeutic interference based on recombinant techniques are discussed.

Allergens↗
PubMed1993

Tumor necrosis factor alpha and interleukin-1 beta mRNA expression in HMC-1 cells: differential regulation of gene product expression by recombinant interleukin-4.

Cytokine-activation pathways in mast cells are supposed to play a significant role in host defense mechanisms and allergic reactions. Interleukin-4 (IL-4) is a well-characterized regulator of growth and function of mast cells. The human mast cell line HMC-1 was established from a patient suffering from mast cell leukemia and was shown to expose IL-4 binding sites. In the present study, the effects of recombinant human (rh) IL-4 and other rh cytokines (IL-2, IL-3, IL-6, IL-8) on expression of cytokine mRNA in HMC-1 cells were examined by Northern blot analysis using oligonucleotide probes. Tumor necrosis factor alpha (TNF-alpha) and IL-1 beta transcripts were found to be expressed constitutively in HMC-1 cells, whereas transcripts for IL-3, IL-4, IL-5, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) could not be detected. Of all cytokines tested, rhIL-4 was found to down-regulate IL-1 beta mRNA expression and formation of immunoreactive IL-1 beta protein in HMC-1 cells. The effect of IL-4 on IL-1 beta gene product expression was time- and dose-dependent (maximum effects obtained with 100 U/mL of rhIL-4). No effect of IL-4 on expression of TNF-alpha mRNA in HMC-1 cells was observed. These results raise the possibility that human mast cells are a source of both TNF-alpha and IL-1 beta. Furthermore, our study provides evidence that IL-4 regulates IL-1 beta gene product expression in HMC-1 cells. The HMC-1 cell line should be a useful tool for studying cytokine activation pathways in human mast cells.

Base Sequence↗
PubMed1992

Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture.

In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF]) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL-3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.

Antibodies, Monoclonal↗
PubMed1992

Type beta transforming growth factors promote interleukin-3 (IL-3)-dependent differentiation of human basophils but inhibit IL-3-dependent differentiation of human eosinophils.

Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.

Antibodies, Monoclonal↗
PubMed1992

Characterization of prostaglandin (PG)-binding sites expressed on human basophils. Evidence for a prostaglandin E1, I2, and a D2 receptor.

Recent data suggest that prostaglandins (PGs) are involved in the regulation of basophil activation. The aim of this study was to characterize the basophil PG-binding sites by means of radioreceptor assays using 3H-labeled PGs. Scatchard analysis for pure (greater than 95%) chronic myeloid leukemia (CML) basophils revealed two classes of PGE1-binding sites differing in their affinity for the natural ligand (Bmax1 = 217 +/- 65 fmol/10(8) cells; Kd1 = 0.5 +/- 0.2 nM; Bmax2 = 2462 +/- 381 fmol/10(8) cells; Kd2 = 47 +/- 20 nM; IC50 = PGE1 less than PGI2 less than PGD2 less than PGE2 less than PGF2 alpha) as well as two classes of PGI2 (iloprost)-binding sites (Bmax1 = 324 +/- 145 fmol/10(8) cells; Kd1 = 0.5 +/- 0.3 nM; Bmax2 = 2541 +/- 381; Kd2 = 27 +/- 6 nM; IC50 = PGI2 less than PGE1 less than PGD2 less than PGE2 less than PGF2 alpha. In addition, CML basophils exhibited a single class of PGD2-binding sites (Bmax = 378 +/- 98 fmol/10(8) cells; Kd = 13 +/- 4 nM; IC50: PGD2 less than PGI2 less than PGE1 less than PGE2 less than PGF2 alpha). In contrast, we were unable to detect specific saturable PGE2-binding sites. Primary and immortalized (KU812) CML basophils revealed an identical pattern of PG receptor expression. Basophils (KU812) expressed significantly (p less than 0.001) lower number of PGE1 (PGI2)-binding sites (Bmax1: 9% (20%) of control; Bmax2: 36% (50%) of control) when cultured with recombinant interleukin 3 (rhIL-3), a basophil-activating cytokine, whereas rhIL-2 had no effect on PG receptor expression. Functional significance of binding of PGs to basophils was provided by the demonstration of a dose-dependent increase in cellular cAMP upon agonist activation, with PGE1 (ED50 = 1.7 +/- 1.1 nM) and PGI2 (ED50 = 2.8 +/- 2.3 nM) being the most potent compounds. These findings suggest that human basophils express specific receptors for PGE1, PGI2 as well as for PGD2.

Alprostadil↗
PubMed1992

In vivo synergism of recombinant human interleukin-3 and recombinant human interleukin-6 on thrombopoiesis in primates.

Using a primate model, we examined the effect of recombinant human interleukin-3 (rhIL-3) and rhIL-6 on thrombopoiesis in vivo. Administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days increased levels of circulating colony-forming units megakaryocyte (CFU-Mk) by approximately 15-fold in five rhesus monkeys without raising their platelet counts. In contrast, administration of 30 micrograms/kg/d of rhIL-6 for 10 days in four animals did not increase CFU-Mk levels but significantly raised platelet counts from a mean pretreatment value of 460 x 10(3)/microL (range 360 to 610) to a mean maximum of 746 x 10(3)/microL (665 to 790) on day 8. If monkeys were pretreated with rhIL-3 (33 or 100 micrograms/kg/d for 11 days) to expand their CFU-Mk compartment, the thrombopoietic effect of rhIL-6 was synergistically enhanced leading to platelet counts above 1,000 x 10(3)/microL (mean maximum value 1,247) in all three primates studied. The sequential administration of rhIL-3 and rhIL-6 might represent a powerful strategy to stimulate thrombopoiesis in vivo.

Animals↗
PubMed1992

Profilins constitute a novel family of functional plant pan-allergens.

Type I allergy is a major health problem in industrialized countries where up to 15% of the population suffer from allergic symptoms (rhinitis, conjunctivitis, and asthma). Previously, we identified a cDNA clone that encoded a birch pollen allergen as profilin. Profilins constitute a ubiquitous family of proteins that control actin polymerization in eukaryotic cells; in particular, profilin participates in the acrosomal reaction of animal sperm cells. Although profilins had been unknown in plants so far, our finding led to the assumption that profilins might have similar functions in pollens during plant fertilization and therefore represent allergenic components in almost all pollens. We show that profilins are prominent allergens that can be isolated from tree pollens (Betula verrucosa, birch), from pollens of grasses (Phleum pratense, timothy grass), and weeds (Artemisia vulgaris, mugwort). About 20% of all pollen allergic patients tested (n = 65) displayed immunoglobulin E (IgE) reactivity to recombinant birch profilin that was expressed in pKK223-3. An IgE inhibition experiment performed with recombinant birch profilin and purified natural profilins from timothy grass and mugwort indicates common IgE epitopes. Moreover, all pollen profilins purified from these far distantly related plant species, and likewise the purified recombinant birch profilin, are able to elicit dose-dependent histamine release via high affinity Fc epsilon receptor of blood basophils from profilin allergic patients. The presence of profilin and possibly related proteins as crossreacting allergenic components in various plants therefore provides an explanation as to why certain allergic patients display type I allergic reactions with pollens and even food from distantly related plants. A functional pan-allergen, like profilin, available as purified recombinant protein, may be a useful diagnostic and probably therapeutic reagent.

Allergens↗
PubMed1992

Treatment of de novo acute myelogenous leukemia with recombinant granulocyte macrophage-colony-stimulating factor in combination with standard induction chemotherapy: effect of granulocyte macrophage-colony-stimulating factor on white blood cell counts.

GM-CSF is a major regulator of myelopoiesis. Recombinant human GM-CSF (250 micrograms/m2 per day i.v.) was used prior to chemotherapy ("3 + 7" scheme) to recruit leukemic blasts in vivo (de novo AML patients, n = 20) into the chemotherapy sensitive phases of the cell cycle. The stimulatory effect of GM-CSF on peripheral blood AML blasts was associated with a rapid redistribution of leukemic blood cells and with an increase in "S-phase positive" cells. Standard induction chemotherapy ("3 + 7") following GM-CSF induced complete aplasia in 19/20 patients. In the same patients, rhGM-CSF (given after chemotherapy) was found to shorten the time of complete aplasia compared to historical controls whereas post-chemotherapy- and follow-up data suggest no significant differences for CCR and survival. Together, our studies show that GM-CSF can safely be administered to AML patients in combination with induction chemotherapy to recruit leukemic cells into the cell cycle.

Adult↗