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Biomedical subjects

E F Knol

Publications and source records attributed to E F Knol.

At least 55 records · Page 3Linked to original sources
PubMed2000

Clinical and immunologic variables in skin of patients with atopic eczema and either positive or negative atopy patch test reactions.

BACKGROUND: 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. OBJECTIVE: 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? METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Animals↗
PubMed2000

Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow's milk allergy: relevance of TH2 cytokines.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Animals↗
PubMed1999

Basophils from patients with allergic asthma show a primed phenotype.

BACKGROUND: IL-3, IL-5, and GM-CSF are not able to induce histamine release in purified basophils of nonallergic donors. However, we have recently found that preincubation with 2 micromol/L thapsigargin, which induces a rise in intracellular free calcium ions, renders human basophils extremely sensitive for IL-3, IL-5, or GM-CSF, leading to enhanced histamine release. Histamine release was also induced in the reverse order (first cytokine and then thapsigargin). OBJECTIVE: Because these cytokines are supposed to be increased in allergic inflammation, we examined whether basophils of patients with allergic asthma showed an enhanced response to thapsigargin. METHODS: We measured the histamine release induced by thapsigargin in a group of allergic asthmatic subjects (n = 24) and compared this response with those of 3 control groups. The control groups consisted of healthy control subjects (group 1, n = 21); patients with a nonallergic, nonasthmatic lung disease (group 2, n = 22); and patients with nonallergic asthma (group 3, n = 9). RESULTS: There was no difference in spontaneous histamine release. Also, no significant difference in histamine release was found when anti-IgE or formyl-methionyl-leucyl-phenylalanine was used as a stimulus. Histamine release induced by IL-3 alone or a combination of IL-3 and thapsigargin also did not differ. In contrast, basophils from the group with allergic asthma showed a significantly higher percentage of histamine release induced by thapsigargin (38.2% +/- 13.2%) than did basophils from the 3 control groups (healthy control subjects, 22.5% +/- 6.9%; subjects with lung disease, 24.9% +/- 8.9%; subjects with nonallergic asthma 15.0% +/- 3.0%; all mean +/- SD). CONCLUSION: These data indicate that basophils in peripheral blood of subjects with allergic asthma have a primed phenotype and that thapsigargin-induced histamine release is a practical tool to study this phenomenon.

Adult↗
PubMed1999

CD11b+ cells and ultraviolet-B-resistant CD1a+ cells in skin of patients with polymorphous light eruption.

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.

Adult↗
PubMed1998

Triple role of platelet-activating factor in eosinophil migration across monolayers of lung epithelial cells: eosinophil chemoattractant and priming agent and epithelial cell activator.

Infiltration of eosinophils into the lung lumen is a hallmark of allergic asthmatic inflammation. To reach the lung lumen, eosinophils must migrate across the vascular endothelium, through the interstitial matrix, and across the lung epithelium. The regulation of this process is obscure. In this study, we investigated the migration of human eosinophils across confluent monolayers of either human lung H292 epithelial cells or primary human bronchial epithelial cells. Established eosinophil chemoattractants (IL-8, RANTES, platelet-activating factor (PAF), leukotriene B4, and complement fragment 5a (C5a)) or activation of the epithelial cells with IL-1beta induced little eosinophil transmigration (<7% in 2 h). In contrast, addition of PAF in combination with C5a induced extensive (>20%) transepithelial migration of unprimed and IL-5-primed eosinophils. Eosinophil migration assessed in a Boyden chamber assay, i.e., without an epithelial monolayer, was only slightly increased upon addition of PAF and C5a. Preincubation of eosinophils with the PAF receptor antagonist WEB 2086 only inhibited migration of unprimed eosinophils toward PAF and C5a, whereas preincubation of epithelial cells with WEB 2086 abolished migration of both IL-5-primed and unprimed eosinophils. This latter result indicated the presence of PAF receptors on epithelial cells. Indeed, addition of PAF to epithelial cells induced an increase in cytosolic free Ca2+, which was blocked by the PAF receptor antagonists WEB 2086 and TCV-309. Our results show that PAF induces permissive changes in epithelial cells, and that PAF acts as a chemoattractant and priming agent for the eosinophils.

Adjuvants, Immunologic↗
PubMed1998

The bactericidal/permeability-increasing protein (BPI) is present in specific granules of human eosinophils.

Eosinophils participate in the inflammatory response seen in allergy and parasitic infestation, but a role in host defense against bacterial infection is not settled. The bactericidal/permeability-increasing protein (BPI) has been demonstrated in neutrophils and it exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. Using the Western blot technique, a 55-kD band, corresponding to BPI, was detected in lysates from both neutrophils and eosinophils. The localization of BPI in immature and mature eosinophils was investigated using immunoelectron microscopy. BPI was found in immature and mature specific granules of eosinophils and was detected in phagosomes as well, indicating release of the protein from the granules into the phagosomes. Using a specific enzyme-linked immunosorbent assay, eosinophils were shown to contain 179 ng of BPI/5 x 10(6) eosinophils compared with 710 ng BPI/5 x 10(6) neutrophils. The presence of BPI in eosinophils suggests a role for these cells in host defense against Gram-negative bacterial invasion or may suggest a role for BPI against parasitic infestation.

Antimicrobial Cationic Peptides↗
PubMed1998

Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2.

Human eosinophils perform several functions dependent on phospholipase A2 (PLA2) activity, most notably the synthesis of platelet-activating factor (PAF) and leukotriene C4 (LTC4). Several forms of PLA2 have been identified in mammalian cells. In the present study, the 14-kD, secretory form of PLA2 was detected in human eosinophils by immunocytochemical staining with the specific monoclonal antibody (MoAb) 4A1. In contrast, preparations of neutrophils, monocytes, lymphocytes, and basophils did not show detectable staining. With two MoAbs in a sandwich enzyme-linked immunosorbent assay (ELISA), large amounts of sPLA2 were detected in lysates of eosinophils, that were 20-fold to 100-fold higher than in the other circulating leukocytes (ie, neutrophils, basophils, monocytes, and lymphocytes). In addition, with a commercially available sPLA2 activity assay kit, we were able to show high activity of sPLA2 in human eosinophils relative to neutrophils. Investigations at the ultrastructural level showed that sPLA2 in eosinophils is mainly located in specific granules. Immunoelectron microscopy also visualized sPLA2 within phagosomes after addition of opsonized particles to the eosinophils. However, sPLA2 was not detected in the cell-free supernatants of activated eosinophils, in contrast to eosinophil-cationic protein (ECP), which colocalizes with sPLA2 in resting eosinophils. These findings warrant further studies into the role of sPLA2 in eosinophil function.

Basophils↗
PubMed1998

Adhesion molecule expression on skin endothelia in atopic dermatitis: effects of TNF-alpha and IL-4.

BACKGROUND: Atopic dermatitis (AD) is characterized by skin infiltrates of leukocytes, such as lymphocytes and eosinophils. OBJECTIVE: To describe the mechanisms determining this inflammatory process, we have analyzed expression of adhesion molecules and their regulation on skin endothelial cells (ECs). METHODS: Expression of adhesion molecules on ECs was analyzed by immunohistochemistry by using Ulex europaeus agglutin 1 as a pan-endothelial marker. RESULTS: Vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin were not found in skin of nonatopic individuals, whereas expression of these surface molecules was observed in nonlesional skin of patients with AD and was even more pronounced in lesional skin or after epicutaneous application of aeroallergen. Induction of adhesion molecule expression was examined on both macrovascular ECs from human umbilical cord vein (HUVECs) and human microvascular ECs (HMEC-1) from skin. TNF-alpha very potently upregulated adhesion molecule expression in vitro on both EC cell types. To verify the in vivo relevance of TNF-alpha, we performed TNF-alpha staining in the skin. TNF-alpha was observed in the dermis of nonatopic skin, both in chymase-containing mast cells and CD68+ macrophages. The increase in the number of TNF-alpha-containing cells was concomitant with the increase in adhesion molecule expression in the skin of patients with AD. IL-4 is supposed to be important in atopic diseases because of its IgE- and VCAM-1-inducing properties. However, IL-4 addition failed to induce VCAM-1 expression on HMEC-1, although in the same set of experiments, a clear induction of VCAM-1 expression by IL-4 on HUVECs was demonstrated. Flow cytometry revealed the absence of 11-4 receptor alpha-chains on HMEC-1 and their presence on HUVECs. Immunohistochemistry examination on skin sections showed no binding of the IL-4R alpha-chain antibodies to ECs. CONCLUSION: We conclude that adhesion molecule expression is increased in the skin of patients with AD. Most probably, this increased expression is not a (direct) effect of IL-4 on skin endothelium, but other cytokines, such as TNF-alpha, might be responsible for this increased adhesion molecule expression. Continuous adhesion molecule expression may facilitate T-cell extravasation in a nonantigen-specific manner, thus explaining the presence of increased T-cell numbers in nonlesional skin of patients with AD.

Cell Adhesion Molecules↗
PubMed1998

Degranulation of human basophils by picomolar concentrations of IL-3, IL-5, or granulocyte-macrophage colony-stimulating factor.

In most secretory cells, an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) is associated with the exocytosis response. In this study we have evaluated the effect of thapsigargin on histamine release from purified (70% to 97% pure) human basophils of nonallergic donors. Thapsigargin (2 micromol/L), by inhibiting the uptake of Ca2+ in the stores of the endoplasmic reticulum, leads within 1 minute to a gradual increase in [Ca2+]i in human basophils. Incubation of basophils with thapsigargin by itself induced only a very small release of histamine (5.6% +/- 1.8%). However, under suboptimal conditions of stimulation with other agonists, preincubation of basophils with thapsigargin significantly enhanced histamine release. Most strikingly, addition of thapsigargin made basophils extremely sensitive for histamine release induced by IL-3 (maximum histamine release, 71% +/- 7%), IL-5 (maximum histamine release, 43% +/- 8%), or granulocyte-macrophage colony-stimulating factor (GM-CSF) (maximum histamine release, 57% +/- 10%). These cytokines by themselves did not induce histamine release in purified basophils. The effect of thapsigargin was mimicked to a limited extent by addition of platelet-activating factor. We conclude that depletion of the Ca2+ stores may be a critical event in the activation of receptor-mediated histamine release in human basophils.

Basophil Degranulation Test↗
PubMed1998

Eosinophil granulocyte interaction with serum-opsonized particles: binding and degranulation are enhanced by tumor necrosis factor alpha.

Eosinophils participate in the inflammatory response seen in allergy and helminthic infestation. Their release of granule-bound cationic proteins may play a role in these diseases. Therefore, we investigated mechanisms involved in the release of eosinophil cationic protein (ECP). Serum-opsonized zymosan was phagocytosed by eosinophils, and ECP was released into the phagosomes as judged by immunoelectron microscopy. Degranulation to the external milieu was induced by serum-opsonized, non-phagocytosable Sephadex beads (SOS), and ECP release was determined by use of an enzyme-linked immunosorbent assay. CD11b, CD18, and CD32 monoclonal antibodies inhibited degranulation, demonstrating dependence on complement receptor type 3 (CR3), and the low-affinity Fc receptor for IgG. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-5 both rapidly enhanced the binding of eosinophils to serum-opsonized zymosan, and also the release of ECP upon interaction with SOS. The cytokine-induced increase in ECP release was inhibited by the phospholipase A2 (PLA2) inhibitor mepacrine, indicating an involvement of PLA2 in the enhanced response but not in baseline degranulation. Autocrine stimulation by the platelet-activating factor (PAF) is unlikely since the PAF receptor antagonist WEB 2086 did not inhibit the enhanced response. In conclusion, the main signals for eosinophil degranulation on serum-opsonized particles are mediated by CR3 and receptors for immunoglobulins. As for IL-5, TNF-alpha changes eosinophil phenotype from a resting to an activated state.

Antibodies, Monoclonal↗
PubMed1997

Human monocytes and neutrophils store transforming growth factor-alpha in a subpopulation of cytoplasmic granules.

Transforming growth factor-alpha (TGF-alpha) exerts several effects on target cells, such as neovascularization promotion and mitogenic signalling. Using immunoelectron microscopy, we show that monocytes and neutrophils, store TGF-alpha in cytoplasmic granules. In monocytes, TGF-alpha did not colocalize with components of peroxidase-positive granules or with albumin of secretory vesicles. Furthermore, no colocalization of TGF-alpha with components of azurophilic or specific granules or secretory vesicles was observed in neutrophils. Activated monocytes and tissue-macrophages contained much less TGF-alpha-positive granules, suggesting TGF-alpha release. Western blot analysis showed a protein of 10 kD in lysates of monocytes. TGF-alpha mRNA was detected in monocytoid cells from the bone marrow by in situ hybridization. This study shows for the first time that monocytes and neutrophils contain TGF-alpha in all stages of maturation and that TGF-alpha in monocytes is stored in a large population of peroxidase-negative granules suggesting a function for these granules. Monocytes and neutrophils are important effector cells in inflammatory reactions. The present finding that these cells contain TGF-alpha might explain complications such as fibrosis and neoplastic transformation, caused by chronic inflammation.

Bone Marrow↗
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↗
PubMed1997

Localization of granule proteins in human eosinophil bone marrow progenitors.

Eosinophils have a characteristic content of cationic proteins, stored in core-containing specific granules and released at sites of inflammation; coreless granules (sometimes called primary) are present in eosinophil promyelocytes. In order to determine a possible relationship between the two granule subsets, immunoelectron-microscopic techniques were used to determine the presence and precise intragranular distribution of major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and arylsulfatase B of eosinophil granules, as well as the Charcot-Leyden crystal (CLC) protein, in eosinophil progenitors of the bone marrow. MBP, ECP, EPO, and arylsulfatase B were observed in both coreless and core-containing (specific) granules. The difference in the distribution of MBP, having a uniform distribution in coreless granules and a crystalloid distribution in core-containing (specific) granules, could indicate a maturational process of a common organelle. CLC protein was distributed in the cytosol, in the euchromatin of the nuclei, but was also present in a rare granular compartment of both immature and mature eosinophils. The present findings suggest that coreless granules develop into core-containing specific granules.

Blood Proteins↗
PubMed1996

Neutrophil transmigration across monolayers of endothelial cells and airway epithelial cells is regulated by different mechanisms.

Neutrophil recruitment from the blood stream into the airways is one of the important features of many inflammatory disorders in the lung. In this process, neutrophils migrate first from the blood across the ECs in the apical-to-basolateral direction into the tissues and then across airway epithelium in the basolateral-to-apical direction into the lung lumen. We investigated and compared the different mechanisms of neutrophil transmigration in vitro across monolayers of these two cell types in both directions. Neutrophil migration induced by chemoattractants was stronger across resting EC than across resting epithelial cells when both cell types were growing on top of the filters (i.e., migration in the apical-to-basolateral direction). Much higher neutrophil transepithelial migration was found in the physiological, basolateral-to-apical direction (cells hanging underneath the filters) than in the opposite direction across either resting or IL-1 beta-activated epithelial cells. In contrast, no significant difference was observed with EC under these conditions. After a 4-h IL-1 beta activation, neutrophil migration across EC was dependent on IL-8 and PAF. However, the migration across epithelial cells relied, to a greater extent, on IL-8 production, and not on PAF. The adhesion molecule ICAM-1 contributed much less to neutrophil migration across epithelium than that across endothelium. Our study provides evidence of different mechanisms of neutrophil transmigration across monolayers of EC and epithelial cells in vitro, indicating that different processes control neutrophil transmigration across EC and epithelial cells in vivo.

Bronchi↗
PubMed1996

Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes.

Eosinophils are involved in the inflammatory response seen in allergy and helminthic infestations. Eosinophils synthesize transforming growth factor-alpha (TGF-alpha), which may play a role in the development of the characteristic fibrosis seen in longstanding high eosinophilia. Using immunoelectron microscopic techniques, eosinophils from peripheral blood of healthy individuals and from one patient with high eosinophilia showed presence TGF-alpha in matrix of the specific crystalloid-containing granules. In cryosections, TGF-alpha was also visualized in a vesicular compartment of the cytoplasm. In double-labeling experiments, the TGF-alpha of this latter compartment did not colocalize with CD63, a marker for lysosomes, nor with albumin of secretory vesicles. In extracts from eosinophils, obtained from healthy donors, immunoreactive TGF-alpha could be detected by enzyme-linked immunosorbent assay-technique. In addition, sera from two patients with high eosinophilia showed TGF-alpha concentrations of 1.5 ng/mL and 164 pg/mL, respectively, whereas TGF-alpha could not be detected in serum from healthy controls. In conclusion, TGF-alpha is present in the specific granules, and in an additional vesicular compartment of the cytoplasm of eosinophils.

Cryoultramicrotomy↗
PubMed1996

Histamine-releasing activity in supernatants of mononuclear cells: contribution of monocyte chemotactic protein-1 activity compared with IgE-dependent activity.

BACKGROUND: Supernatants of cultured human mononuclear cells contain factors that induce histamine release from basophils. Some of the histamine-releasing factors present are IgE-independent, but an IgE-dependent form has also been described. The IgE that does respond to the IgE-dependent histamine-releasing factor was defined as IgE+. OBJECTIVE: This study was conducted to analyze the contribution of chemokines, such as monocyte chemotactic protein-1 (IgE-independent), to improve the detection of IgE-dependent histamine-releasing factor. METHODS: Supernatants were prepared from mononuclear cells of three subjects. Monocyte chemotactic protein-1 content and histamine-releasing activity (HRA) were measured. Depletion of chemokine activity was carried out with heparin-Sepharose (Pharmacia, Uppasala, Sweden). RESULTS: Replacing IgE- on basophils with IgE+ serum decreased the correlation between monocyte chemotactic protein-1 and histamine release (rho = 0.80, n = 280 vs p = 0.12, n = 18; p for difference between p values; < 0.05). After depletion of chemokines in three supernatants derived from mononuclear cells, IgE-dependent HRA was still present. CONCLUSION: We conclude that in supernatants derived from mononuclear cells, the IgE-independent HRA masks the IgE-dependent HRA. The latter can be more clearly detected after depletion of chemokine activity with heparin-Sepharose.

Animals↗
PubMed1996

Reactivity to IgE-dependent histamine-releasing activity in asthma or rhinitis.

We investigated the relation between IgE reactive with histamine-releasing factor (HRF) and clinical status in patients with asthma or rhinitis. Sera were used to passively sensitize purified, lactic-acid treated basophils. IgE-independent HRF due to chemokines was removed from mononuclear cell supernatants with heparin-Sepharose. IgE-dependent HRF was determined by measuring the increase in histamine release between 1 min and 60 min, which was designated delta HRF. HRF-reactive IgE was demonstrable in nine of 18 patients with allergic asthma, three of 19 patients with nonallergic asthma, five of 17 patients with allergic rhinitis, and none of 19 control patients. The presence of HRF-reactive IgE was associated with: (1) IgE to inhalant allergens; 40% of radioallergosorbent test (RAST)-positive individuals versus 8% of RAST-negative individuals were positive (OR = 7.8, p < 0.005); (2) bronchial sensitivity to histamine in all asthmatic patients (geometric mean PC20: 1.50 versus 0.51 mg/ml; p < 0.005); and (3) bronchial sensitivity to histamine in allergic asthmatic patients (geometric mean PC20: 1.27 versus 0.37 mg/ml, p < 0.02). These findings support the hypothesis that IgE-dependent HRF might contribute to the chronic allergic reaction.

Adolescent↗