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[Value of basophil studies in the diagnosis of drug allergies].

Mastocytes and basophils are the two cell populations involved in the reactions seen during drug allergies. The testing of basophils is the only and simplest way of studying sensitization in the IgE system by a drug antigen, especially when the skin tests cannot be carried out. This study is carried out in two steps: straight after the drug-induced accident, where a basophil count will give an idea of its allergic origin; and some time after the accident, where the human basophil degranulation test (H.B.D.T.) helps to identify in over 50 p. 100 of cases the responsible drug. The basophil count and H.B.D.T. techniques are then described. The authors present their own results. In a study by H.B.D.T. of 908 patients with a drug allergy, 53.2 p. 100 had positive test; 57.6 p. 100 of 33 cases who presented an anaesthetic accident had a positive H.B.D.T.

Anesthetics↗

Kinetics of mast cell, basophil and eosinophil populations at Hyalomma anatolicum anatolicum feeding sites on cattle and the acquisition of resistance.

The cutaneous cellular reactions associated with acquisition of resistance by cattle to Hyalomma anatolicum anatolicum feeding were investigated by comparing the nature and sequence of cellular events at H.a. anatolicum feeding sites following primary and tertiary infestations. Cattle acquired resistance to H.a. anatolicum feedings after a single infestation. The resistance was manifested by a significant reduction in the mean weight of engorged females and mean weight of egg mass produced, failure to lay eggs and sometimes death of ticks in situ. The acquisition of resistance corresponded with pronounced epidermal vesiculation and a significant change in the nature of the cellular infiltrate at tick feeding sites indicating the development of cutaneous hypersensitivity. On primary infestation the cellular infiltrate was dominated by neutrophils (43-71%) followed by mononuclear cells (25-35%). Basophil and eosinophil infiltration in small numbers was noticed for the first time at 72 and 144 h, respectively, post-primary infestation. Unlike primary infestation, the dermal infiltrate on tertiary infestation, 24 h after attachment, was characterized by infiltration of basophils (6%) and eosinophils (3%) and a marked degranulation of mast cells and basophils. Basophils showed a consistent increase in absolute as well as relative numbers as the feeding advanced. They were the second most abundant cell types after neutrophils (48-68%) at 72 h (16%), and 144 h (23%). Eosinophils (3-9%) and mononuclear cells also showed a significant increase in their mean numbers as compared with primary infestation. There was a progressive decrease in the number of detectable mast cells following tick infestation and they were significantly lower post-tertiary infestation, compared to primary infestation. These results suggest that the pharmacological mediators released by degranulation of mast cells and basophils are perhaps the major effectors of resistance in cattle to H.a. anatolicum.

Animals↗

Basophil activation during pollen season in patients monosensitized to grass pollens.

BACKGROUND: Basotest is a new basophil-activation test based upon the expression of CD63 (gp53) in the presence of allergens. It is an effective diagnostic test for pollen-allergic patients. However, it is not known whether Basotest results differ during the pollen season. METHODS: We examined the activation of basophils by Basotest in 13 patients sensitized only to grass pollen, before and during the pollen season, in order to assess whether Basotest could be used as a diagnostic test during the pollen season. Dose-response curves with 10-fold increasing concentrations of timothy grass pollen (10-4 to 100 AU) were carried out. RESULTS: Basophils were not activated spontaneously during the pollen season since the CD63 expression was below detectable levels before in vitro cell activation. A decreased percentage of activated basophils at the peak of activation was found in comparing the pre- and in-season tests, but all patients had a positive test. When basophil activation was at its peak, the allergen concentration was similar during the two periods. Moreover, the median area under the curve was significantly (P < 0.02) reduced during the season as compared to before the season. CONCLUSION: Basotest can therefore be used as a diagnostic test during the pollen season, but the allergen exposure needs to be characterized if quantitative studies are performed.

Adult↗

Validation of a two-color flow cytometric assay detecting in vitro basophil activation for the diagnosis of IgE-mediated natural rubber latex allergy.

BACKGROUND: IgE-dependent triggering of basophils not only elicits the release of different mediators but also the up-regulation of certain markers, e.g. CD63, which can be detected by flow cytometry. We intended to investigate if flow cytometric analysis of basophil activation could be a valuable tool in the diagnosis of latex allergy, and to evaluate if the basophil activation test (BAT) could be helpful in determining the clinical significance of a positive latex IgE in individuals with negative history and negative latex skin test. Additionally we aimed to determine the role of cross-reactive carbohydrate determinants (CCDs) in causing positive latex IgE without apparent clinical significance. METHODS: Twelve healthy controls without a history of latex hypersensitivity with a negative latex IgE and skin test (group 1), 24 individuals without a history of latex hypersensitivity with a negative latex IgE and skin test but with other inhalant allergies (group 2), and 29 latex allergic patients with a compelling history of latex allergy with a positive latex IgE and prick test (group 3) were enrolled. The diagnostic performances of the BAT were further evaluated in 13 individuals with a history of latex allergy but with negative specific IgE and/or skin test (group 4). Twenty-four individuals with positive latex IgE without apparent clinical relevance, i.e. without history of latex hypersensitivity and negative latex skin tests, were also analyzed (group 5). The putative role of CCDs causing positive latex IgE results without apparent clinical significance was evaluated by quantification of IgE for bromelain. RESULTS: According, to the receiver operating characteristics(ROC)-generated threshold value of 17% between latex allergic patients and the pooled group of nonlatex allergic individuals, the sensitivity and specificity of the basophil activation test was 93.1% and 91.7%, respectively. In healthy controls, allergic patients without latex hypersensitivity and latex allergic patients the number of positive BATs was 0/12, 3/24 and 27/29, respectively. In the individuals with an evocative history of latex allergy but with negative latex IgE and/or skin test the BAT was positive in all 13 cases. Twenty of 24 individuals without apparent latex allergy but with positive latex IgE had a negative BAT. IgE for bromelain was positive in 1/19 sera from group 2, 1/24 sera from group 3, none of the 8 sera from group 4, but in 16/18 sera from group 5, respectively. CONCLUSION: Flow cytometric analysis of activated basophils seems a highly sensitive and specific tool for diagnosing latex allergy. In addition, the technique might help to determine the clinical relevance of positive IgE quantification in the absence of overt latex allergy. CCDs of natural rubber latex allergens were confirmed to mimic latex sensitization.

Basophils↗

Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-dependent upregulation.

Using two-colour flow cytometry >200 antibodies submitted to the 8th International Workshop of Human Leukocyte Differentiation Antigens (HLDA8) have been analyzed for their reactivity with resting and activated CD203c+ basophils. Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor (FceRI). These include antibodies against CD164 (WS-80160, clone N6B6 and WS-80162, clone 67D2), as well as two reagents with previously unknown specificities that were identified as CD13 (WS-80274, clone A8) and CD107a (WS-80280, clone E63-880). The activation patterns followed either the "CD203c-like" or "CD63-like" activation profile. The CD203c profile is characterized by a rapid and significant upregulation (of CD13, CD164, and CD203c), reaching maximum levels after 5-15 min of stimulation. The Phosphoinositide-3-kinase (PI3K)-specific inhibitor Wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced a rapid and FceRI-independent upregulation within 1-2 min. In the CD63 profile, maximum upregulation (of CD63 and CD107a) was detected only after 20-40 min, and upregulation by TPA reached maximum levels after 60 min. In summary, our data identify CD13, CD107a, and CD164 as novel basophil-activation antigens. Based on time kinetics of upregulation, we hypothesize that molecules of the "CD203c group" and the "CD63 group" are linked to two different mechanisms of basophil activation.

Androstadienes↗

Macrophage inflammatory protein-1alpha and C-C chemokine receptor-1 in allergen-induced skin late-phase reactions: relationship to macrophages, neutrophils, basophils, eosinophils and T lymphocytes.

BACKGROUND: Macrophage inflammatory protein (MIP)-1alpha binds to C-C chemokine receptor (CCR)-1 with high affinity. CCR-1 is expressed on neutrophils, eosinophils, monocytes, T lymphocytes and basophils; cells characteristic of atopic allergic inflammation. In vitro, MIP-1alpha is chemotactic for monocytes, T cells and basophils and is also a potent histamine-releasing factor for basophils and mast cells. Although increased levels of MIP-1alpha were shown in atopic allergic disorders, the kinetics of expression of these CC chemokines in vivo is largely unknown. OBJECTIVE: To investigate the kinetics of expression of MIP-1alpha and receptor CCR-1 and the relationships between the expression and infiltration of inflammatory cells in allergen-induced cutaneous late-phase reactions in atopic subjects. METHODS: Cryostat sections, obtained from skin biopsies from 10 human atopic subjects at 6, 24, 48, 72 h and 7 days after allergen challenge, were processed for immunohistochemistry and in situ hybridization using 35S-labelled riboprobes. RESULTS: The peak expression of allergen-induced mRNA for MIP-1alpha and CCR-1 was 6 h. This was maintained at 24 h, and gradually returned to base line at 7 days. At 6 h, the number of cells expressing MIP-1alpha mRNA significantly correlated with elastase+ neutrophils and BB-1+ basophils. At 24 h, the MIP-1alpha mRNA+ cells significantly correlated with CD68+ macrophages. There were significant inverse correlations between the numbers of MIP-1alpha mRNA cells and the numbers of Tryptase+ mast cells at 6 and 24 h after allergen challenge. CONCLUSION: Allergen-induced cutaneous late-phase reactions in humans were associated with increased expression of MIP-1alpha and CCR-1. This may be relevant to the infiltration of neutrophils, eosinophils, basophils and macrophages.

Basophils↗

Coding single nucleotide polymorphism in the high-affinity immunoglobulin E receptor b chain (FcepsilonRI-beta) gene is associated with immunoglobulin E receptor-mediated histamine release from basophils.

BACKGROUND: Our previous work on linkage analysis showed that histamine release from basophils to anti-IgE stimuli was linked to the gene marker of chromosome 11q13, where the beta chain of the high-affinity receptor for IgE (FcepsilonRI-beta) is located. OBJECTIVE: To evaluate the association between FcepsilonRI-mediated histamine release from basophils and four bi-allelic single nucleotide polymorphisms of the FcepsilonRI-beta gene. METHODS: Phenotypes of asthma, such as maximal histamine release from basophils and atopy, were measured from 80 randomly recruited asthmatic children. Polymorphisms of the FcepsilonRI-beta gene were determined by PCR-based methods. RESULTS: The polymorphism in exon 7, resulting in Glu to Gly substitution, was significantly associated with histamine release from basophils to anti-IgE stimuli, but not with total IgE levels and skin test responses to aeroallergens. CONCLUSION: This study supports a role for the FcepsilonRI-beta gene in the expression of high affinity IgE receptor-mediated histamine release from basophils.

Adolescent↗

Allergen-specific conventional immunotherapy decreases immunoglobulin E-mediated basophil histamine releasability.

BACKGROUND: Allergen-specific immunotherapy has proven to be clinically effective in the treatment of patients with atopic asthma; however, the mechanisms are still unclear. Several noted immunological changes include an increase of the allergen-specific IgG antibody, a reduction in the allergen-specific IgE antibody subsequent to transient increase, an allergen-specific T cell shift in cytokine production from Th2 to Th1, and a decrease in quantity and activity of basophils and mast cells. OBJECTIVE: To analyse the changes of basophil histamine release in response to IgE-mediated and non-IgE-mediated stimuli before and after conventional house-dust mite immunotherapy in children who suffer from atopic asthma. METHODS: Fourteen Dermatophagoides farinae (Df) sensitive asthmatic children with conventional immunotherapy were examined. Basophil histamine releasability was measured 0 months (just before immunotherapy), 4 months and 9 months after immunotherapy. Basophils were stimulated with Df and goat anti-human IgE antibody as IgE-mediated stimuli; and formyl-Met-Leu-Phe (fMLP) and calcium ionophore A23187 as non-IgE-mediated stimuli. Accordingly, the asthma symptom score was used to assess clinical outcome and the skin test reactivity to Df was measured. RESULTS: In contrast to pre-immunotherapy activity, 4 and 9 months after immunotherapy there were significant decreases in histamine release by Df and by anti-IgE antibody. The histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. Histamine release by Df demonstrated significant correlation to that by anti-IgE antibody and by fMLP, yet there was no observable correlation between histamine release by Df and by calcium ionophore. The asthma symptom score decreased significantly 4 and 9 months after immunotherapy and showed significant correlation with histamine release by Df. The skin test reactivity (allergen/histamine ratio) remained constant 4 months after immunotherapy, but decreased significantly 9 months after immunotherapy. CONCLUSION: Basophils have the potential to play an important role in the early clinical improvement of conventional immunotherapy in children with atopic asthma, which may be a result of the decreased IgE-mediated histamine releasability during immunotherapy.

Adolescent↗

Granulocyte-macrophage colony-stimulating factor and interleukin-3 cause basophil histamine release by a common pathway: downregulation by sodium.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are recognized as enhancers, but not as inducers, of histamine release from normal human basophils. However, when extracellular Na+ is removed IL-3 acquires the capacity to induce histamine release. The aim of this study was to evaluate whether GM-CSF can induce basophil histamine release using the same pathway of IL-3. Leucocyte suspensions from normal human subjects were stimulated with GM-CSF, IL-3 and anti-IgE, and histamine release was evaluated by an automated fluorometric method. In a physiological medium, GM-CSF (10 ng/ml) and IL-3 (10 ng/ml) did not provoke histamine release, in spite of an efficient response to anti-IgE (10 micrograms/ml). However, when extracellular Na+ was substituted iso-osmotically with N-methyl-d-glucamine+ or with choline+, GM-CSF and IL-3 were able to trigger histamine release from either mixed leucocyte suspensions or purified human basophils. The effect of GM-CSF on basophil histamine release was dose dependent, with optimal release at a dose of 1 ng/ml after incubation at 37 degrees for 60-120 min. The kinetics of IL-3-induced histamine release were similar, whereas anti-IgE-induced histamine release was more rapid, being almost maximal after incubation for 30 min. A good correlation was found between GM-CSF-induced and IL-3-induced histamine release; furthermore, the combined effects of the two cytokines were less than additive, suggesting that they share the same pathways leading to histamine release. When extracellular Na+ concentration was increased from 0 to 140 mm, histamine release induced by GM-CSF, IL-3 and anti-IgE was reduced progressively. In contrast, histamine release induced by these stimuli was upregulated when the concentration of extracellular Ca2+ was increased. These results provide indirect evidence that GM-CSF and IL-3 can induce basophil histamine release by a common pathway that is downregulated by Na+.

Adult↗

Spontaneous release of histamine from basophils and histamine-releasing factor in patients with atopic dermatitis and food hypersensitivity.

Patients with hypersensitivity to food documented by a double-blind, placebo-controlled oral food challenge have been reported to have a high rate of release of histamine from basophils in vitro. To determine whether patients with atopic dermatitis and food hypersensitivity had similar high rates of spontaneous histamine release in vitro, whether dietary elimination of relevant food antigens affected this release, and whether a cytokine, histamine-releasing factor, could account for it, we evaluated 63 patients with atopic dermatitis and food hypersensitivity (38 of whom had eliminated the offending foods from their diets), 20 patients with atopic dermatitis without food hypersensitivity, and 18 normal volunteers. Patients with atopic dermatitis and food hypersensitivity were found to have higher rates of spontaneous release of histamine from basophils than controls (mean +/- SE, 35.1 +/- 3.9 percent vs. 2.3 +/- 0.2 percent; P less than 0.001). Those who had eliminated the offending food allergen from the diet for an extended period had a significantly lower rate of histamine release (3.7 +/- 0.5 percent; P less than 0.001). In patients with atopic dermatitis without food hypersensitivity, the rate (1.8 +/- 0.2 percent) did not differ from that in normal controls. Mononuclear cells from persons with food allergies spontaneously produced a histamine-releasing factor in vitro that provoked the release of histamine from the basophils of other food-sensitive persons, but not from those of normal controls. Patients who adhered to a restricted diet had a decline in the rate of spontaneous generation of the factor by their mononuclear cells. The histamine-releasing factor was found to activate basophils through surface-bound IgE. We conclude that in patients with food hypersensitivity, exposure to the relevant antigens produces a cytokine (histamine-releasing factor) that interacts with IgE bound to the surface of basophils, causing them to release histamine.

Adolescent↗

The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils.

BACKGROUND: The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) has recently been developed as a novel and cell-selective inhibitor of inflammatory cytokine secretion; it has fewer adverse effects than currently available drugs. OBJECTIVE: In this study, we investigated the capacity of pimecrolimus to directly inhibit in vitro mediator release from human skin mast cells and basophils. METHODS: Purified cutaneous mast cells or basophil-containing peripheral blood leukocytes were obtained from healthy human donors and preincubated with pimecrolimus (0.1 nmol/L to 1 micromol/L) in the absence or presence of its specific antagonist (rapamycin), cyclosporin A (100 nmol/L to 1 micromol/L), or dexamethasone (1 micromol/L) and then stimulated with anti-IgE or with calcium ionophore A23187 plus phorbol myristate acetate. Cell supernatants were kept for analysis of histamine, tryptase, LTC4, and TNF-alpha. RESULTS: Pimecrolimus caused a strong and dose-dependent inhibition of anti-IgE--induced release of histamine from mast cells and basophils (maximally 73% and 82%, respectively, at 500 nmol/L pimecrolimus) and of mast cell tryptase (maximally 75%) and a less pronounced inhibition of LTC4 (maximally 32%) and of calcium ionophore plus phorbol myristate acetate--induced mast cell TNF-alpha release (90% maximum at 100 nmol/L pimecrolimus). In contrast, inhibition achieved during mast cell histamine release was maximally 60% with cyclosporin A and only 28% with dexamethasone. CONCLUSION: These data demonstrate a marked inhibitory capacity of pimecrolimus on mediator release from human mast cells and basophils with a potency exceeding that of cyclosporin A and dexamethasone. Pimecrolimus might thus be expected to be effective in the treatment of mast cell-- and basophil-dependent diseases.

Anti-Inflammatory Agents, Non-Steroidal↗

Recombinant allergens promote expression of CD203c on basophils in sensitized individuals.

BACKGROUND: Traditionally, the diagnosis of type I allergies is based on clinical data, skin test results, and laboratory test results with allergen extracts. During the past few years, several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation. OBJECTIVES: We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE receptor cross-linkage. In this study we applied CD203c and a panel of recombinant allergens to establish a novel basophil test that allows for a reliable quantification of IgE-dependent responses at the effector cell level. METHODS: Patients allergic to birch (Bet v 1, n = 15; Bet v 2, n = 8) and grass (Phl p 1, n = 15; Phl p 2, n = 10; Phl p 5, n = 14) pollen allergens, as well as 10 nonallergic donors, were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by means of flow cytometry. CD203c upregulation was correlated with the increase in CD63. RESULTS: Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase was seen in healthy control subjects. The effects of the recombinant allergens on CD203c expression were also time dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R = 0.76). CONCLUSION: Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergy test.

Allergens↗

Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line.

We report the cloning and characterization of a novel basophil CC chemokin receptor, K5-5, from the human immature basophilic cell line KU-812. The predicted protein sequence of K5-5 shows only 49% identity to the macrophage inflammatory protein-1 alpha/RANTES receptor (CC CKR-1) and 47% identity to monocyte chemotactic protein-1 receptor (b form), suggesting that this cDNA encodes a novel member of the CC chemokine receptor family. Analysis of K5-5 mRNA expression indicates that it is restricted to leukocyte-rich tissues. In addition, we have shown significant levels of K5-5 mRNA in human basophils, which were up-regulated by treatment with interleukin-5. The CC chemokines, Macrophage inflammatory protein-1 alpha, RANTES, and monocyte chemotactic protein-1 were able to stimulate a Ca(2+)-activated chloride channel in Xenopus laevis oocytes injected with K5-5 cRNA, whereas no signal was detected in response to monocyte chemotactic protein-2, macrophage inflammatory protein-1 beta, or the CXC chemokine, interleukin-8. Taken together, these results indicate for the first time the presence of a CC chemokine receptor on basophils, which functions as a "shared" CC chemokine receptor and may therefore be implicated in the pathogenesis of basophil-mediated allergic diseases.

Amino Acid Sequence↗

Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels.

In this study, we identify the bidirectional organic cation transporter 3 (OCT3/Slc22a3) as the molecule responsible for histamine uptake by murine basophils. We demonstrate that OCT3 participates in the control of basophil functions because exogenous histamine can inhibit its own synthesis--and that of interleukin (IL)-4, IL-6, and IL-13--through this means of transport. Furthermore, ligands of H3/H4 histamine receptors or OCT3 inhibit histamine uptake, and outward transport of newly synthesized histamine. By doing so, they increase the histamine content of basophils, which explains why they mimic the effect of exogenous histamine. These drugs were no longer effective in histamine-free histidine decarboxylase (HDC)-deficient mice, in contrast with histamine itself. Histamine was not taken up and lost its inhibitory effect in mice deficient for OCT3, which proved its specific involvement. Intracellular histamine levels were increased strongly in IL-3-induced OCT3-/- bone marrow basophils, and explained why they generated fewer cytokines than their wild-type counterpart. Their production was enhanced when histamine synthesis was blocked by the specific HDC inhibitor alpha-fluoro-methyl histidine, and underscored the determinant role of histamine in the inhibitory effect. We postulate that pharmacologic modulation of histamine transport might become instrumental in the control of basophil functions during allergic diseases.

Animals↗

Evidence for lack of promotion of the growth of the common naturally occurring basophilic focal hepatocellular proliferative lesions in aged F344/NCr rats by phenobarbital.

Aged female F344/NCr rats were exposed to phenobarbital (PB), 500 p.p.m. in the drinking water, from 26 months of age, for periods of 4, 8 or 9-27 weeks. In groups of control and PB-exposed rats sacrificed at these time periods the number and volume of basophilic and eosinophilic focal hepatocellular proliferative lesions (FHPL), including altered foci and adenomas in hematoxylin- and eosin-stained sections and FHPL identified histochemically by their content of gamma-glutamyl transpeptidase (GGT), were determined using computerized image analysis. Tritiated thymidine [3H]TdR was injected prior to sacrifice to determine labeling indices (LI) of normal hepatocytes and hepatocytes in FHPL. Rats receiving PB had significantly increased numbers and volumes of eosinophilic and GGT-positive FHPL while the numbers and volumes of the common basophilic FHPL seen in controls were not affected by PB exposure. The LI of all FHPL were higher than that of normal hepatocytes, but PB exposure did not affect the LI of basophilic FHPL. An uncommon GGT-positive FHPL found in control rats was detected in zone 1 of the hepatic acinus, a similar location of the GGT-positive eosinophilic FHPL seen in PB-exposed rats, while the common basophilic FHPL was observed in zones 1-3. These findings suggest that PB does not promote the growth or development of the common naturally occurring basophilic FHPL but either promotes the uncommon GGT-positive FHPL or induces new FHPL de novo.

Adenoma↗

Cutaneous basophil hypersensitivity.

Cutaneous basophil hypersensitivity is a distinct form of hypersensitivity reaction with a delayed-time course that is different from both the classic delayed-type hypersensitivity reaction and immediate hypersensitivity reaction. It occurs in humans, guinea pigs, and other animals. It may be induced by sensitization with a variety of antigens (viruses, allografts, parasites, fungal antigens, etc.) in incomplete Freund's adjuvant and elicited by skin testing 7 days later with the specific antigens. The cutaneous reaction in basophil hypersensitivity is characterized clinically by less indurated erythema than in classic delayed hypersensitivity, and microscopically by numerous basophils in the papillary dermis. The reaction is mediated by both T- and B-lymphocytes. A basophil chemotactic factor as a mediator of the reaction has also been identified. The reaction may be inhibited by Fc fragments. Basophils on arrival at the local site may degranulate and the released vasoamine may have protective or regulatory effects depending on particular circumstances.

Animals↗

Basophil releasability in young highly trained and older athletes.

PURPOSE: Exercise-induced hypoxemia in highly trained athletes is associated with an increase in histamine release during exercise. The cells most implicated in blood histamine release are basophils. The aim of this study was to determine whether high-level endurance training induces modifications in histamine releasability from human basophils. METHODS: Seven young highly trained athletes (YA) [aged 26.1+/-1.3 yr (mean +/- SEM)] and seven master athletes (MA) (64.4+/-4.1 yr), all known to develop exercise-induced hypoxemia, were respectively compared with seven young untrained men (YC) (23.0+/-1.5 yr) and seven older untrained men (OC) (61.6+/-1.3 yr). During an incremental exhaustive exercise, blood samples for measurement of anti-IgE-induced histamine release from leukocytes were drawn at rest, VO2max, and recovery. RESULTS: Basophils from "leukocyte-rich" supernatant in YA and MA showed significantly higher histamine release induced by anti-IgE (1 microg x mL(-1) than, respectively, YC (P<0.01) and OC (P<0.05) at rest, VO2ax (P<0.01), and recovery (P<0.01). Basophils in YA and MA also showed a histamine release induced by anti-IgE that was higher at VO2max than at rest (respectively. P<0.01 and P<0.05), but this change was not found in the control groups. CONCLUSION: In conclusion, the basophils in highly trained endurance athletes, both young and older, showed higher anti-IgE-induced histamine release than those of untrained men. This effect of high-level training seemed to be potentiated by exercise.

Adult↗

Value of the cutaneous basophil hypersensitivity (CBH) response for distinguishing weak contact sensitization from irritation reactions in the guinea pig.

Numerous studies of the histology of allergic contact dermatitis reactions to potent allergens in guinea pigs and humans have indicated that there is significant tissue infiltration with basophilic leukocytes. In this study we determined whether this histologic finding could be of value in distinguishing weak sensitization reactions from primary irritation, thereby aiding in the predictive identification of weak or moderate contact allergens. Guinea pigs were sensitized by the Buehler test method. Skin reactions were graded 24, 48, and 72 h post-challenge with duplicate patch sites biopsied at the 24- or 72-h grading timepoints. The biopsies were fixed, embedded in glycol methacrylate, thin sectioned, and Giemsa stained. The number of basophils per 400 leukocytes were counted along the upper dermis just below the dermal/epidermal junction. Challenge patch sites from animals sensitized to a relatively low dose of the strong contact allergen, oxazolone, were compared with patch sites from animals challenged only with a strong irritant, sodium lauryl sulfate (SLS). Compared to normal skin (7.5 +/- 1.0 basophils/400 leukocytes +/- SEM) only the oxazolone patch sites showed significant basophil infiltration (36.8 +/- 6.5), despite the fact that the skin reactions to the low oxazolone challenge dose were relatively weak. SLS patch sites showed no basophil infiltration above normal skin levels (4.8 +/- 0.9). Subsequent blinded studies compared weak/moderate presumptive sensitization reactions (as defined by accepted visual skin grading criteria) to various chemicals (citronellal, vanillin, cinnamic aldehyde, and ethylenediamine) to primary irritation reactions to the same chemicals. In each case, low-challenge-dose sensitization sites on previously treated (induced) animals showed mean basophil infiltration (range, 11.9-69.2 basophils/400 leukocytes) significantly greater than higher-dose irritant reactions (range, 1.6-13.3). The range for normal skin was 0.2-10.2 and the range for strong patch reactions to higher concentrations of oxazolone was 59.8-209.3. These data strongly indicate that light-microscopic quantitation of the CBH response can be used to distinguish relatively weak to moderate contact sensitization reactions from primary irritation reactions to the same chemicals.

Animals↗