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ABSTRACT: The diagnostic value of hazelnut allergy tests in double-blind challenged children is largely unknown. The aim of this study was to analyze the performance of current diagnostic tests for hazelnut allergy in children and the effect of spiking.
Data of 151 children who underwent a double-blind placebo-controlled food challenge for hazelnut were analyzed. The positive predictive value and negative predictive value (PPV/NPV) of level of specific IgE (sIgE) for hazelnut, the influence of rCor a 1 spiking of the ImmunoCAP, and size of the skin prick test (SPT) for hazelnut were determined, also in relation to the severity of the hazelnut allergy. Reported accidental ingestion leading to an allergic reaction to hazelnut was also analyzed in relation to hazelnut allergy.
Specific IgE ≥0.35 kU(A) /l for hazelnut was a moderate predictor for hazelnut allergy. The spiking decreased the PPV from 41% to 38% and increased the NPV from 91% to 100% for sIgE ≥0.35 kU(A) /l. The maximum reached PPV was 73% for sIgE cutoff of 26 kU(A) /l. Level of sIgE before spiking was significantly different between different grades of severity and was lost after spiking. Skin prick test was a better predictor for hazelnut allergy and severity than the level of sIgE. A history of accidental ingestion leading to an allergic reaction to hazelnut had a predictive value of 59% for hazelnut allergy.
This study showed a good NPV of diagnostic tests for hazelnut allergy in children which further improved by rCor a 1 spiking. However, the PPVs are moderate and decreased by spiking.
Allergy 12/2011; 67(4):521-7. · 6.27 Impact Factor
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J.Allergy Clin.Immunol. 01/2011; 127(1).
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ABSTRACT: In peanut-allergic adults, IgE is mainly directed to Ara h1 and Ara h2. More recently, a role for Ara h6 has been suggested. In contrast to adults, IgE in children can fluctuate over time. Therefore, children may have a more dynamic reactivity to peanut.
To examine the IgE reactivity to major peanut allergens in peanut-allergic children at two subsequent time-points.
Twenty children (3-15 years old) with peanut allergy, confirmed by a double-blind placebo-controlled food challenge (DBPCFC), were included. Just before and 20 months after DBPCFC, IgE reactivity to purified Ara h1, Ara h2, Ara h3 and Ara h6 was studied by immunoblots and skin prick tests (SPTs).
Before DBPCFC, all peanut-allergic children showed IgE reactivity to Ara h2; Ara h6 was recognized by 16 children, and Ara h1 and Ara h3 by 10 children. After 20 months, peanut-specific IgE levels (median 23 kU/L) and the individual recognition of major allergens were comparable with the levels and recognition before challenge (median 28.2 kU/L). SPT with Ara h2 and Ara h6 was positive in most children, whereas SPT with Ara h1 and Ara h3 was positive in approximately half of the children. Ara h6 induced the largest weals. None of the parameters were related to the severity of peanut allergy.
Ara h2 and Ara h6 are the most frequently recognized major peanut allergens in children. The individual reactivity to the major peanut allergens remained stable over time, despite DBPCFC.
Clinical & Experimental Allergy 09/2007; 37(8):1221-8. · 5.03 Impact Factor
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S.T. Bolhaar,
W.E. Van de Weg,
van Ree R.,
E. Gonzalez-Mancebo,
L. Zuidmeer, C.A. Bruijnzeel-Koomen,
M. Fernandez-Rivas,
J. Jansen,
K. Hoffmann-Sommergruber,
A.C. Knulst,
L.J. Gilissen
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ABSTRACT: BACKGROUND: Apple cultivars have been reported to differ in allergenicity on the basis of in vitro and skin prick tests with apple extracts. OBJECTIVES: We sought to evaluate the efficacy of the prick-to-prick method in assessing differences in allergenicity of apple cultivars and to confirm differences by means of double-blind, placebo-controlled food challenge (DBPCFC). METHODS: Intra-assay and intracultivar variation of prick-to-prick test results were determined in 6 Dutch and 8 Spanish patients with apple allergy by using 5 apples of the cultivars Golden Delicious, Fuji, and Ecolette in duplicate. In addition, 21 cultivars were screened for allergenicity in 15 Dutch patients with birch pollen and apple allergy. Two selected cultivars (Golden Delicious and Santana) were tested with DBPCFCs. The influence of storage conditions on allergenicity was assessed in 5 cultivars. RESULTS: Intra-assay variation of skin prick testing was 3.9%, and intracultivar variation was 4.1%. A ranking of 21 cultivars was made on the basis of prick-to-prick tests in 9 patients. Apple cultivars were classified as of low, intermediate, and high allergenicity, with a significant difference between low and high allergenicity (P < .001). A significant difference in allergenicity determined between Golden Delicious and Santana cultivars (P < .05) was confirmed by means of DBPCFC. With 5 cultivars, controlled atmosphere (2.5% oxygen/1% carbon dioxide) was shown to reduce allergenicity (P < .001) by 15% compared with storage at 2 degrees C. CONCLUSIONS: Prick-to-prick testing with fresh apples is a reproducible method of assessing allergenicity. Apples can be classified as of low or high allergenicity for the majority of patients. This was confirmed by using DBPCFCs. Selection of cultivars and control of storage conditions are both viable strategies for reduction of symptoms in patients with apple allergy
J.Allergy Clin.Immunol. 11/2005; 116(5).
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S.T. Bolhaar,
M.M. Tiemessen,
L. Zuidmeer,
A. van Leeuwen,
K. Hoffmann-Sommergruber, C.A. Bruijnzeel-Koomen,
L.S. Taams,
E.F. Knol,
E. van Hoffen,
R. van Ree,
A.C. Knulst
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ABSTRACT: BACKGROUND: The effect of birch-pollen immunotherapy (IT) on cross-reactive food allergies is controversial. OBJECTIVE: The aim of this study was to investigate the effect of birch-pollen IT on apple allergy and to evaluate recombinant allergens and double-blind placebo-controlled food challenges (DBPCFCs) as monitoring tools. METHODS: Twenty-five adult birch-pollen- and apple-allergic patients were randomly divided into two groups, either receiving birch-pollen IT or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple, natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT) were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1). Clinical outcome was evaluated by DBPCFC. CD4(+)CD25(+) regulatory T cells (Tregs) were isolated from peripheral blood and tested in functional assays. RESULTS: Birch-pollen IT resulted in a significant decrease of SPT reactivity for rBet v 1 (30-fold) and rMal d 1 (10-fold) already after 3 months. IgG4 antibodies were potently induced against Bet v 1, displaying cross-reactivity to Mal d 1. Visual analogue scale scores decreased >10-fold in 9/13 patients of the IT group, with three patients converting to negative. In the control group, no decrease was observed. Birch-pollen IT did not lead to detectable changes in the number or function of the CD4(+)CD25(+) Tregs. CONCLUSIONS: This trial supports the claims that birch-pollen IT also decreases allergy to foods containing Bet v 1-homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful tools for monitoring the effect of birch-pollen IT on linked food allergies
Clin Exp Allergy. 05/2004; 34(5).
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ABSTRACT: Macrophages and dendritic cells may play a role in chronicity of atopic dermatitis (AD); however, so far only limited data are documented on the distribution of these cells in the skin during cutaneous inflammation.
To gain better insight into the presence and distribution of macrophage and dendritic cell (sub)populations in acutely and chronically inflamed skin of AD patients.
Chronic inflammatory reactions were studied in lesional AD skin biopsies; the atopy patch test was used as a model for the initiation of AD lesions, representing acute inflammation. To determine the number and phenotype of different dermal macrophage and dendritic cell populations immunohistochemistry and digital imaging were used.
There was an increase in macrophage numbers in acutely and chronically inflamed AD skin, whereas absolute dendritic cell numbers were unchanged, compared with non-lesional AD skin. Furthermore, phenotypically heterogeneous and overlapping macrophage and dendritic cell populations were present in inflamed AD skin. The classic macrophage marker CD68 and prototypic dendritic cell marker CD1a could bind to the same cell subpopulation in the dermis of inflamed AD skin. Mannose receptors were expressed mainly by macrophages in inflamed AD skin.
In this study we observed changes in macrophage number and phenotype during cutaneous inflammation in AD. Dendritic cell numbers did not change; however, phenotypically dendritic cell and macrophage subpopulations showed increasing overlap during inflammation in AD skin. We show for the first time that within tissue-specific macrophage populations further subpopulations are present, and that monocyte-derived cells may express markers for both dendritic cells and macrophages. Our results point to the existence of a heterogeneous pool of macrophage/dendritic cell-like cells, from which subpopulations of dermal macrophages and dendritic cells arise.
British Journal of Dermatology 01/2002; 145(6):957-65. · 3.67 Impact Factor
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Allergy 03/2001; 56(2):191-2. · 6.27 Impact Factor
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ABSTRACT: The serology of peanut allergy seems to be different in various parts of the world. We analyzed the composition of 13 samples of three varieties of peanut in order to compare their allergenic nature.
Peanut cultivars that are commonly processed in the West were analyzed for protein content, protein composition, and Ara h 1 and Ara h 2 content by biochemical methods. IgE-binding properties were analyzed by ELISA using serum from patients with documented peanut allergy.
Total protein contents were comparable for all tested samples (24-29%), and proteins were extractable to the same extent. SDS-PAGE patterns differed slightly, but all major bands were visible in all samples (molecular masses of approximately 14100 kDa under reducing conditions). Ara h 1 and Ara h 2 were quantified by SDS PAGE densitometry and were expressed as percentage of the total protein content. Ara h 1 was in the range 12-16%, whereas Ara h 2 was 5.9-9.3%. In view of the analytic uncertainty of this determination, the content of both Ara h 1 and Ara h 2 was not significantly different between the tested samples. In an IgE-binding inhibition ELISA, the affinities of the peanut proteins for peanut-specific IgE were measured. Minor differences were observed between the tested samples, with the most potent IgE-binding sample having a two times higher ability to bind IgE than the weakest IgE-binding sample.
The results suggest that peanuts of different varieties and from different parts of the world contain similar proteins, including Ara h I and Ara h 2. Consequently, the IgE-binding properties are similar to a great extent. This indicates that differences in the serology of peanut allergy may not originate from differences in the allergen composition of the peanut.
Allergy 03/2001; 56(2):132-7. · 6.27 Impact Factor
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ABSTRACT: Cow's milk is the most important food antigen in infancy and may lead to acute cutaneous symptoms and atopic dermatitis (AD). The role of circulating allergen-specific T cells in the pathogenesis of food-allergic skin symptoms is still under investigation.
This study was designed to analyze the cow's milk protein (CMP)-specific T-cell response at the clonal level in infants with AD and cow's milk allergy (CMA) in comparison with infants with AD without CMA.
We used an antigen-specific culturing system with autologous B cells as antigen-presenting cells to establish CMP-specific T-cell clones derived from PBMCs in infants with AD. T-cell reactivity, measured by using a lymphocyte stimulation test, and cytokine production, measured by using ELISA, was compared between infants with AD with and without CMA.
Both infants with and without allergy to cow's milk had a CMP-specific T helper cell response directed against the major proteins in milk. Analysis of antigen-specific cytokine production showed that this response was T(H)2 skewed in infants with CMA, with production of high levels of IL-4, IL-5, and IL-13. In contrast, infants without CMA had a T(H)1-skewed response, with high levels of IFN-gamma and low levels of IL-4, IL-5, and IL-13.
These data confirm for the first time at the clonal level that food allergy in infants with AD is associated with production of T(H)2 cytokines by circulating antigen-specific CD4(+) T cells, whereas tolerance to food antigens is associated with low levels of these cytokines. This suggests a key role for the T helper cell-derived T(H)2 cytokines in food allergy-related skin symptoms.
Journal of Allergy and Clinical Immunology 01/2001; 106(6):1155-62. · 11.00 Impact Factor
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ABSTRACT: Erythroderma, or generalized erythema of the skin, may result from different causes. At present it is unclear whether the underlying patho-mechanisms that lead to erythroderma are identical or different depending on the original disease. The aim of this study was to investigate the dermal cytokine profile in different types of erythroderma and mycosis fungoides.
Snap-frozen skin biopsy specimens from 33 patients with erythroderma were studied. Thirteen had idiopathic erythroderma, 7 erythrodermic atopic dermatitis, 5 Sézary syndrome and 8 had erythroderma from miscellaneous causes. We also studied 6 patients with mycosis fungoides (5 plaques and 1 tumor) and 5 healthy non-atopic volunteers. The biopsies were immunohistochemically stained for interleukin 4 (IL-4) and interferon gamma (IFN-gamma). All positive cells for IL-4 and IFN-gamma in the dermis were counted and the number of positive cells was calculated per mm2. IL-4/IFN-gamma ratio was calculated for each biopsy.
The patients with idiopathic erythroderma, atopic dermatitis and miscellaneous erythroderma, all showed more IFN-gamma-positive cells than IL-4-positive cells in the dermis. The median IL-4/ IFN-gamma ratio for these three groups was 0.6, 0.9 and 0.45, respectively. These differences were not statistically significant. All patients with Sézary syndrome however, showed more IL-4-positive cells than IFN-gamma-positive cells. The median IL-4/IFN-gamma ratio was 1.8, which is significantly higher than in the other groups p<0.05). In mycosis fungoides roughly the same number of cells expressed IL-4 and IFN-gamma. The median IL-4/IFN-gamma ratio was 1.0, which is significantly lower than in Sézary syndrome (p<0.05).
The dermal infiltrate in patients with Sezary syndrome mainly shows a T-helper 2 (Th2) cytokine profile, this in contrast to T-helper 1 (Th1) cytokine profile in benign reactive erythroderma. This indicates that although a relative uniform clinical picture of erythroderma is obvious, a different patho-mechanisms may be underlying.
Journal of Cutaneous Pathology 11/2000; 27(9):429-35. · 1.56 Impact Factor
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ABSTRACT: Erythroderma may result from different causes. At present it is unclear whether the patho-mechanisms that lead to these different types of erythroderma are identical or different. Adhesion molecules and their ligands play a major role in endothelial-leukocyte interactions, which affect the binding, transmigration and infiltration of lymphocytes and mononuclear cells during inflammation, injury, or immunological stimulation. The aim of this study was to investigate the adhesion molecule expression on endothelial cells in erythroderma in situ.
Snap-frozen skin biopsy specimens from 23 patients with erythroderma were studied. Eight had idiopathic erythroderma, 5 erythrodermic atopic dermatitis, 4 Sézary syndrome and 6 had erythroderma from miscellaneous causes. As a control we studied skin specimens from 10 patients with mycosis fungoides, 5 patients with atopic dermatitis and 5 healthy non-atopic volunteers. To determine adhesion molecule expression on endothelial cells in situ, sections were immuno-histochemically double stained with biotinylated Ulex Europaeus agglutinin 1 as a pan-endothelial cell marker, and for the adhesion molecules VCAM-1, ICAM-1, E-, and P-selectin. All double- and single-stained blood vessels in the dermis were counted.
Mean endothelial expression in erythroderma was as follows: VCAM-1 51.4%, ICAM-1 70.1%, E-selectin 43.5%, and P-selectin 52.6%. There was no statistical difference between different groups of erythroderma. Mean expression of all adhesion molecules tested, was in Sézary syndrome higher than in mycosis fungoides albeit not significant. In erythrodermic atopic dermatitis only VCAM-1 expression was significantly higher than in lesional skin of atopic dermatitis. No differences were observed in expression of the other three adhesion molecules.
There is no difference regarding adhesion molecule expression on endothelial cells between different types of erythroderma.
Journal of Cutaneous Pathology 11/2000; 27(9):436-40. · 1.56 Impact Factor
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ABSTRACT: Pharmacologic studies in atopic eczema (AE) are difficult to standardize. Patients with AE differ in the stage of their skin disease (acute, subacute, chronic).
This study was designed to assess macroscopic and microscopic effects of pretreatment with topical glucocortico-steroids (GCSs) and tar on the atopy patch test (APT) reaction in patients with atopic eczema.
Nonlesional skin of the back of patients with AE (n = 6) was treated for 3 weeks at 3 different sites with triamcin-olonacetonide 0.1% in cetamacrogol ointment (GCSs), pix liquida 10% in cetamacrogol ointment (tar), and cetamacrogol ointment (vehicle), respectively. APTs were performed, and biopsy specimens were taken from all these sites (time = 0 and 24 hours) for immunohistochemical analysis.
Treatment with both GCSs and tar was able to reduce the macroscopic outcome of the APT reaction. Furthermore, both treatment modalities had an almost equally inhibiting effect on the influx of T cells, eosinophils, and CD1(+), RFD1(+), IFN-gamma(+), and IL-4(+) cells, as well as on the percentage of vessels expressing the adhesion molecules vascular cell adhesion molecule 1 and E-selectin in response to epicutaneous aeroallergen challenge.
Although both treatments significantly reduced the various cellular constituents of allergic inflammation, all cell types remained present. In addition, this study shows that the APT can be used to evaluate the effect of topical anti-inflammatory treatments on allergic inflammation in patients with AE.
Journal of Allergy and Clinical Immunology 11/2000; 106(4):737-43. · 11.00 Impact Factor
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ABSTRACT: Atopic dermatitis is an allergic skin disease characterized by elevated total and antigen-specific serum IgE and IgG4 levels. In acute and chronic cutaneous inflammation, large cellular infiltrates including T cells, dendritic cells and macrophages are found, especially in the dermis. These cells play an important part in the regulation of local inflammatory reactions. Receptors binding IgG (FcgammaR) are involved in dendritic cell and macrophage function. In this study, we examined the in vivo distribution and cellular expression of the three classes of leucocyte FcgammaR in human skin during acute and chronic cutaneous inflammation in atopic dermatitis. Atopy patch test skin was used as a model for acute inflammation in atopic dermatitis, while chronic lesional skin was used to investigate FcgammaR expression in chronically inflamed skin. In atopy patch test sites no increase in the number of CD1a+ dendritic cells and a slight increase in macrophages compared with non-lesional skin was observed. Our results showed increased expression of FcgammaRI (CD64) and FcgammaRIII (CD16) in acutely inflamed skin as well as in chronically inflamed lesional skin, compared with healthy and non-lesional atopic dermatitis skin. FcgammaRI was expressed by RFD1+, RFD7+ and CD68+, but not by CD1a+ dermal dendritic cells. RFD1+ dendritic cells and CD68+ macrophages were the main FcgammaRIII-expressing cells during the acute inflammatory reaction. The significant increase in expression of FcgammaRIII (CD16) and FcgammaRI (CD64) probably results from upregulation of the receptors on resident cells. Insight into the presence of FcgammaR+ cells in human skin during inflammation is important both for our understanding of skin immune reactions and the development of new therapeutic concepts.
British Journal of Dermatology 07/2000; 142(6):1106-13. · 3.67 Impact Factor
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ABSTRACT: Epicutaneous application of aeroallergens induces a positive atopy patch test (APT) response in about 50% of patients with atopic eczema (AE) and sensitization for these allergens.
To elucidate the mechanisms determining the outcome of the APT, the following questions were addressed. Are there differences in clinical features between patients with AE who have positive versus negative APT responses? Is a macroscopically negative APT response also histologically negative, and if so, are there differences in clinically noninvolved skin between the two groups regarding (1) the sensitivity toward an irritant, (2) the composition of cellular infiltrate, (3) the presence of aeroallergen-specific T cells, and (4) the number of IgE(+) cells?
Punch biopsy specimens from both house dust mite patch tested and the clinically noninvolved skin of patients with AE who have positive APT responses (n = 10) and negative APT responses (n = 10) and those from the normal skin of atopic individuals without AE (n = 10) and nonatopic volunteers (n = 10) were analyzed by using immunohistochemistry with mAbs against eosinophil cationic protein, IgE, the high-affinity receptor for IgE, and CD3 and CD25 mAbs. Furthermore, T-cell lines were propagated from noninvolved skin of all patient and control groups. The T-cell lines were tested for house dust mite specificity.
Negative APT sites were immunohistochemically similar to clinically noninvolved AE skin. There were no significant differences between patients with AE who had positive and negative APT results regarding either clinical features, the composition of cellular infiltrate, or the presence of allergen-specific T cells in clinically noninvolved skin. However, differences were observed regarding the presence of IgE on epidermal CD1a(+) cells.
Our results indicate that a positive APT reaction requires the presence of epidermal IgE(+) CD1a(+) cells in clinically noninvolved skin, but that also other, as yet unknown, discriminatory factors are involved.
Journal of Allergy and Clinical Immunology 06/2000; 105(5):1008-16. · 11.00 Impact Factor
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Allergy 09/1999; 54(8):784-91. · 6.27 Impact Factor
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ABSTRACT: After ultraviolet exposure Langerhans cells (epidermal CD1a+ cells) disappear from the healthy skin, and CD11b+ macrophage-like cells, which are reported to produce interleukin-10, appear in a matter of days. These phenomena are related to the ultraviolet-induced local suppression of contact hypersensitivity reactions. A defect in this suppression might allow inadvertent immune reactions to develop after ultraviolet (over)exposure; i.e., it could cause ultraviolet-B-induced polymorphous light eruption. In order to test this we first exposed buttock skin of eight healthy volunteers to six minimal erythema doses from Philips TL12 lamps, and indeed observed a dramatic disappearance of CD1a+ cells 48 and 72 h later, at which time the number of CD11b+ cells increased in the dermis, and some occurred in the epidermis. The epidermis thickened and showed large defects, filled by CD11b+ cells, just below the stratum corneum. In 10 patients with polymorphous light eruption (five with a normal minimal erythema dose and five with a low minimal erythema dose) CD1a+ cells were present in the epidermis as well as in the dermis before exposure. Strikingly, these cells were still present in considerable number at 48 and 72 h after exposure to six minimal erythema doses. CD11b+ cells already present in the dermis before ultraviolet exposure, increased after ultraviolet exposure, and subsequently also invaded the epidermis. Despite the six minimal erythema doses, there were no apparent defects in the epidermis of the polymorphous light eruption patients. This deviant early response to ultraviolet radiation is likely to be of direct relevance to the polymorphous light eruption and is perhaps useful as a diagnostic criterion.
Journal of Investigative Dermatology 08/1999; 113(1):4-10. · 6.31 Impact Factor
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Allergy 07/1999; 54(6):649-50. · 6.27 Impact Factor
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ABSTRACT: Sézary syndrome (SS) is a rare cutaneous T-cell lymphoma. SS usually develops de novo. We describe a 23-year-old man with a proven history of severe atopic dermatitis since childhood, who developed SS. This case contributes to the discussion about the possibility of a relationship between inflammatory dermatitis, atopy and subsequent SS. We provide criteria that should be fulfilled to define such an association.
British Journal of Dermatology 05/1999; 140(4):704-7. · 3.67 Impact Factor
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ABSTRACT: Ara h 1, a major peanut allergen was isolated, and its structure on secondary, tertiary, and quaternary level at ambient temperature was investigated using spectroscopic and biochemical techniques. Ara h 1 appeared to be a highly structured protein on a secondary level, possesses a clear tertiary fold, and is present as a trimeric complex. Heat treatment of purified Ara h 1 results in an endothermic, irreversible transition between 80 and 90 degreesC, leading to an increase in beta-structures and a concomitant aggregation of the protein. Ara h 1 from peanuts that were heat-treated prior to the purification procedure exhibited a similar denatured state with an increased secondary folding and a decreased solubility. The effect of heat treatment on the in vitro allergenic properties of Ara h 1 was investigated by means of a fluid-phase IgE binding assay using serum from patients with a clinically proven peanut allergy. Ara h 1 purified from peanuts heated at different temperatures exhibited IgE binding properties similar to those found for native Ara h 1, indicating that the allergenicity of Ara h 1 is heat-stable. We conclude that the allergenicity of Ara h 1 is unaffected by heating, although native Ara h 1 undergoes a significant heat-induced denaturation on a molecular level, indicating that the recognition of conformational epitopes of Ara h 1 by IgE either is not a dominant mechanism or is restricted to parts of the protein that are not sensitive to heat denaturation.
Journal of Biological Chemistry 03/1999; 274(8):4770-7. · 4.77 Impact Factor
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ABSTRACT: Similar to interleukin-3 (IL-3), IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF), IL-4 can be secreted by several cell types involved in allergic inflammatory reactions, and therefore can affect eosinophil function similarly. In this study, we investigated the presence of an IL-4 receptor (IL-4R) on human eosinophils. When two different monoclonal antibodies (mAbs) against the IL-4R alpha-chain (IL-4Ralpha) were used, fluorescent-activated cell sorter analysis revealed the presence of an IL-4Ralpha on both eosinophils of normal donors and atopic dermatitis patients. In addition, the expression of the IL-2R gamma-chain, a functional component of the IL-4R in some cell types, was demonstrated. The IL-4Ralpha appeared to be expressed constitutively, and stimulation with cytokines IL-2, IL-3, IL-5, GM-CSF, and interferon-gamma did not further increase IL-4Ralpha expression. Evidence for an IL-4Ralpha was further substantiated by mRNA analysis. Both Northern blot analysis and reverse transcriptase/polymerase chain reaction revealed the presence of mRNA for the IL-4Ralpha in eosinophils from normal individuals and AD patients. Furthermore, we demonstrated that both IL-4 and IL-13 were capable of inducing PI-3 kinase activity in human eosinophils. Because this activation could be inhibited by an IL-4Ralpha mAb, we conclude that both cytokines can activate human eosinophils through binding to a receptor complex comprising the IL-4Ralpha and-yet to be identified-associated proteins. In addition, the involvement of IL-4 in functional responses was studied. IL-4 appeared to "prime" eosinophils to respond chemotactically toward regulated on activation, normal T cells expressed and secreted, but did not affect platelet-activating factor-induced chemotaxis. Taken together, these data show the presence of a functional IL-4R on human eosinophils.
American Journal of Respiratory Cell and Molecular Biology 11/1998; 19(4):691-9. · 5.13 Impact Factor
