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PubMed1979

Basophil chemotaxis under agarose: variability among guinea pig donors and response to sera of different species.

Guinea pig basophils were tested against chemotactic factor(s) generated from homologous and heterologous sera. An "under agarose" method of quantitating leukocyte chemotaxis was adapted to measure serum-derived basophil chemotactic factor(s) (BCF). The method was found to be simple, reproducible, and sparing of time and reagents and it provided simultaneous controls. Because of the economy of reagents compared with the Boyden chamber technique, basophils from individual guinea pigs could be studied and were found to be variable in responsiveness. A definite difference in the response of guinea pig basophils to zymosan-activated sera of various other species was demonstrated. Guinea pig basophils responded to zymosan-activated serum from guinea pig and rat but failed to respond to zymosan-activated serum from human, hamster, rabbit, or cow. Optimal conditions were determined for cell numbers, serum activation and dilution, and migration times for studies of guinea pig BCF. The under agarose technique provides a practical alternative to chamber methods for the study of basophil chemotaxis. Although guinea pig basophils do not respond to human serum-derived BCF, the economy of reagents with this technique gives promise toward adaptation of the method to studies of human basophil chemotaxis.

Animals↗
PubMed1988

Properties of human basophils isolated by fluorescence-activated cell sorting.

The aim of the current study was twofold: (1) to consider the applicability of fluorescence-activated cell sorting (FACS) to basophil isolation from small blood volumes and (2) to compare basophils obtained from children with asthma to basophils from healthy children. With FACS, basophil suspensions were prepared with a purity of 84% (range, 75% to 95%) and a recovery of 20% (range, 15% to 30%). The purified basophils had a total histamine content of 1.6 +/- 0.12 pg per cell, not differing significantly from total histamine content observed in "total" leukocyte suspensions (1.4 +/- 0.07 pg per basophil). The same was true for IgE receptor-mediated histamine release (29 +/- 4% versus 27 +/- 4%) and for ionophore A23187-induced histamine release (41 +/- 6% versus 51 +/- 9%). Sorted basophils from subjects with asthma released more histamine after IgE receptor activation (0.67 +/- 0.09 pg per cell) than basophils from healthy children (0.40 +/- 0.04 pg per cell; p less than 0.02). Expressed as percent release, no significant difference was observed (37 +/- 3.2% versus 30 +/- 2.7%). Ionophore A23187-induced histamine release did not differ significantly between subjects with asthma and control subjects, neither expressed as picograms per cell (1.21 +/- 0.17 pg per cell versus 1.02 +/- 0.11 pg per cell) nor expressed as percent release (66 +/- 4.4% versus 74 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗
PubMed1993

Purification of human blood basophils and leukotriene C4 generation following calcium ionophore stimulation.

A simple method for purification of basophils from a relatively small volume of blood has been developed, which enables us to collect basophils with a purity of over 80%. Basophils were partially purified from 10-20 ml of citrated whole blood using the discontinuous Percoll density gradient centrifugation technique and then contaminant cells were removed using monoclonal antibodies against CD2, CD19, CD14 and CD16. At the end of the procedure, basophils were > 80% pure with lymphocytes accounting for most of the contaminating cells. When stimulated with anti-IgE or fMLP, histamine release from purified basophils was similar to that from mixed leukocytes. When highly purified basophils were challenged with calcium ionophore A23187, generation of leukotriene C4 (LTC4) was not significantly different between asthmatic patients and normal subjects (45.6 +/- 22.6 vs 52.7 +/- 25.6 ng/10(6) cells). Basophils were capable of generating LTC4 in approximately the same quantities as eosinophils (46.5 +/- 11.7 ng/10(6) cells, n = 3). Furthermore, it has been shown that incubation of basophils and eosinophils with calcium ionophore generates only small quantities of thromboxane B2 (TXB2).

Antibodies, Anti-Idiotypic↗
PubMed2003

IFN-alpha inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release.

BACKGROUND: Innate immune responses play a critical role in determining the course of acquired immunity, including that associated with allergic disease. Type I interferons, which are generated early in these reactions, are important soluble factors that prime for TH1-like activity. OBJECTIVE: Because human basophils secrete IL-4 and IL-13 in response to both IgE-dependent and IgE-independent stimuli, we tested whether IFN-alpha, a major type I IFN, affects the production of these TH2 cytokines and/or mediator release from these cells. METHODS: Basophils isolated from blood were treated with IFN-alpha in the presence and absence of IL-3 priming before stimulating through the IgE receptor to release histamine, leukotriene C4, and IL-4. Effects of IFN-alpha on IL-3-mediated IL-13 secretion and basophil survival were also tested. IFN-alpha receptor expression was determined by RT-PCR. RESULTS: IFN-alpha specifically inhibited the effects IL-3 has on basophil cytokine secretion. Enhanced secretion of IL-4 resulting from IL-3 priming was significantly inhibited in cells concurrently cultured with IFN-alpha. This effect was specific for cytokine generation, because histamine and leukotriene C4 were unaffected. Furthermore, IFN-alpha blocked IL-13 secretion directly induced by IL-3. Although IFN-beta also possessed some inhibitory activity, IFN-gamma (a type II IFN) had no effect on basophil cytokine secretion. Basophils constitutively expressed mRNA for the type I IFN receptor, and IFN-alpha did not affect basophil viability with regard to inhibition of cytokine secretion. CONCLUSIONS: These results support the belief that early innate immune responses resulting in IFN-alpha production negatively regulate allergic responses by also inhibiting priming of basophil cytokine release.

Adult↗
PubMed1992

Intracellular events in anti-IgE nonreleasing human basophils.

Histamine release (HR) after activation of human basophils with anti-IgE demonstrates a great variability among different donors. To elucidate the biochemical basis of this phenomenon, we studied the activation of purified basophils from donors that barely demonstrated HR (less than 7%) after stimulation by anti-IgE, although IgE was present on these cells and formyl-methionyl-leucyl-phenylalanine (fMLP)-induced HR was normal. Basophils from anti-IgE "nonreleasers" demonstrated, in contrast to cells from "releasers," hardly any changes in cytosolic-free Ca++ concentration after addition of anti-IgE. However, anti-IgE treatment of basophils from these anti-IgE nonreleasers resulted in at least two intracellular changes. First, a profound inhibition (54.2% +/- 4.2%) of a subsequent fMLP-induced HR was observed. This inhibition caused by anti-IgE was also observed in basophils from anti-IgE releasers treated with wortmannin, an inhibitor of the anti-IgE-induced HR. The time course of the inhibition induced by wortmannin plus anti-IgE on the fMLP-induced HR (half-life maximum, 4 minutes; time of maximum concentration, 10 minutes) was comparable to the time course of the anti-IgE-induced HR. Second, anti-IgE did induce homotypic aggregation in these anti-IgE-nonreleasing basophils, like in anti-IgE-releasing basophils. These studies indicate that basophils not responding to anti-IgE with HR or cytosolic-free Ca++ concentration changes do generate intracellular signals that inhibit the subsequent response to a heterologous stimulus and induce homotypic aggregation.

Antibodies, Anti-Idiotypic↗
PubMed1995

Chemokines of the alpha, beta-subclass inhibit human basophils' responsiveness to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.

Monocyte chemotactic and activating factor (MCAF) is the most potent cytokine that activates basophils to release histamine. The response of human basophils to either simultaneous or sequential addition of the chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, platelet factor (PF)4, connective tissue activating peptide III (CTAP-III), interleukin (IL)-8, and inflammatory protein (IP)-10 on MCAF-induced histamine release was studied. Simultaneous addition of MCAF and any of the chemokines studied evoked an augmented response as measured by histamine release, whereas preincubation of leukocytes or purified basophils (80%) with these chemokines decreased MCAF-induced histamine release in a dose-dependent manner. Histamine release by anti-IgE remained unchanged. When tested at 5 x 10(-9) mol/L, the decrease in histamine release by RANTES was 69.2% +/- 3.5%, by MIP-1 alpha 48.8% +/- 3.1%, by MIP-1 beta 42.9% +/- 3.1%, by PF4 56.5% +/- 2.9%, by IL-8 41.2% +/- 2.2, by CTAP III 27% +/- 4.4%, and by IP-10 15.3% +/- 2.6%. The peak inhibition of histamine release by the chemokines was reached within 10 minutes of preincubation with basophils and remained unchanged thereafter. Washing basophils after preincubation with chemokines abolished the inhibition, with the exception of desensitization by low concentrations of MCAF. With the exclusion of MCAF and RANTES, none of the chemokines (at the concentration range of 5 x 10(-8) to 5 x 10(-11)) induced significant (> 10% above spontaneous) histamine release from basophils. Preincubation of basophils with C5a (5 x 10(-10) mol/L) did not affect histamine release, whereas preincubation with granulocyte-macrophage colony-stimulating factor (10 ng/ml) or IL-5 (10 ng/ml) enhanced MCAF-induced histamine release by 121.8% +/- 10.1% and 108% +/- 10.8%, respectively. We have therefore characterized RANTES, MIP-1 alpha, MIP-1 beta, CTAP III, PF4, IL-8, and IP-10 as inhibitors of MCAF-induced histamine release. Although the results are consistent with receptor blockade, the alpha and beta chemokines appear to interact with separate receptors linked to G proteins; thus, a mechanism of receptor class desensitization is proposed. Interaction of this group of cytokines at the site of allergic inflammation may modulate a function of basophils to initiate, augment, or inhibit histamine release.

Basophils↗
PubMed2003

In vitro expansion of human basophils by interleukin-3 from granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

BACKGROUND: A number of studies support the belief that human basophils play an important role in allergic inflammation. The exact mechanism of basophil activation at the site of allergic inflammation, however, has not been well understood, mainly due to their low number in blood and difficulty in obtaining a sufficient number of highly purified basophils for investigation. OBJECTIVE: The purpose of this study is to expand human basophils in vitro with high yield and purity by culturing peripheral blood stem cells (PBSCs). METHODS: We collected PBSC-rich mononuclear cells containing CD34+ cells (0.15-4.9%) by leukapheresis from patients with malignant lymphoma and lung cancer during haematopoietic recovery after chemotherapy plus granulocyte colony-stimulating factor-induced mobilization. PBSC-rich mononuclear cells were cultured in the presence of IL-3. RESULTS: When PBSC-rich mononuclear cells containing more than 1% of CD34+ cells were cultured, 20.0-83.3% of the cells, mostly with a yield of >10%, were metachromatic cells after 3 weeks of culture. These cells resembled mature peripheral blood basophils morphologically when examined by light and electron microscopy. Flow cytometric analysis showed that they expressed both FcepsilonRI and FcgammaRII. FcepsilonRI cross-linking resulted in intracellular calcium mobilization, histamine release and synthesis of cysteinyl leukotrienes. The intracellular histamine content and the release of these chemical mediators triggered by anti-IgE antibodies were comparable to those of peripheral blood basophils. CONCLUSION: These findings suggest that PBSC-derived basophils expanded in vitro are morphologically and functionally mature and will be a useful tool for the analysis of basophil functions.

Adolescent↗
PubMed1998

Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation.

By generating human mast cells and basophils from umbilical cord blood mononuclear cells cultured in the presence of appropriate cytokines, we investigated whether these two cultured cells could provide the cytokine and cell contact signals that are required to induce IgE synthesis in B cells. To activate cultured mast cells and basophils, cross-linking of cell surface high-affinity IgE receptor (Fc epsilonRI) was performed with specific antigen after sensitization with murine IgE. Upon Fc epsilonRI stimulation, basophils, but not mast cells, secreted significant amounts of immunoreactive IL-4 and IL-13 and expressed detectable CD40 ligand (CD40L) and a very low level of Fas ligand (FasL). These observations at the protein level were consistent with the data obtained at the gene transcriptional level, except for the faint expression of only IL-13 mRNA in mast cells. When added to normal human B cells, activated basophils induced IgE and IgG4 synthesis as well as soluble CD23 release. In contrast, neither IgE nor IgG4 synthesis could be induced by the interaction of B cells with activated mast cells, even in the presence of recombinant IL-4. The induction of IgE synthesis by activated basophils was completely abrogated by two neutralizing MoAbs against IL-4 and IL-13 and by a soluble form of CD40. This abrogation was accompanied by abolished mature C epsilon transcription in both cases. Addition of anti-FasL MoAb, however, did not significantly affect IgE induction mediated by activated basophils. These results demonstrate that unlike cultured mast cells, cultured basophils produce biologically active IL-4 and IL-13 and express functional CD40L after Fc epsilonRI stimulation, thereby contributing to IgE production by B cells, and suggest that relatively weak expression of FasL by cultured basophils is not involved in IgE regulation.

B-Lymphocytes↗
PubMed2001

Quantitative, phenotypic, and functional evaluation of basophils in myelodysplastic syndromes.

BACKGROUND: The myelodysplastic syndromes (MDS) are a group of clonal haematological disorders characterized by cytopenia(s), reduced differentiation-capacity of myeloid cells, and impaired leukocyte function. However, little is known so far about basophil granulocytes in MDS. DESIGN: We have compared the numbers, phenotype and function of basophils in MDS patients with those in healthy subjects. A total numer of 23 patients with MDS (refractory anaemia, n = 8; refractory anaemia with ringsideroblasts, n = 7; refractory anaemia with excess of blasts/refractory anaemia with excess of blasts in transformation, n = 8) and 20 healthy donors were included. RESULTS: The numbers of blood basophils in MDS patients (34.6 +/- 62.9 microL-1) was lower compared to healthy controls (58.6 +/- 64.9 microL-1). Correspondingly, whole blood histamine levels were lower in MDS patients (MDS 34.1 +/- 29.1 ng mL-1 vs. normal donors 72.0 +/- 36.9 ng mL-1). Like "normal" basophils, basophils in MDS expressed interleukin-3 receptor alpha (CD123), E-NPP3 (CD203c), CR1 (CD35), CR3 (CD11b), CR4 (CD11c), membrane co-factor protein (CD46), decay-accelerating factor (CD55) and membrane attack complex inhibitory factor (CD59), as well as receptors for C3a, C5a (CD88), and IgE. Recombinant human (rh) C5a and anti-IgE induced significant release of histamine from basophils in both groups of donors without significant differences between MDS and healthy controls. CONCLUSIONS: The absolute numbers of basophils in MDS patients are lower than in normal donors. However, basophils in MDS do not differ from their "normal counterparts" in terms of complement receptor expression, IgE-receptor expression, or functional responses to respective ligands.

Aged↗
PubMed2003

Influence of the diluent on the effect of highly diluted histamine on basophil activation.

BACKGROUND: In modern pharmaceutical practice, it is common to use purified ethanol and purified water for the preparation of homeopathic dilutions. Hahnemann in 1827 recommended good brandy as a diluent. Brandy contains a lot of accompanying substances in addition to ethanol. PURPOSE OF THE STUDY: The research question was whether different diluents influence the effectiveness of high dilutions, especially above Avogadro's number. We compared two dilution media to investigate the diluent's influence. Within the limitations of the test-system, the dilution media were as similar to good brandy as possible and like purified ethanol. Dilutions of histamine were prepared with both media. As test-system, we used modified basophil activation in an in vitro cell system. Basophils are activated by anti-immunoglobulin E (anti-IgE). The activation of basophils is inhibited by prior incubation with histamine. The reduction in activation was measured with different dilutions of histamine. The test system used a 3-colour flow cytometric method. The interleukin-3 (IL-3) receptor CD123 was used to identify basophils in the leukocyte mixture. The CD63 surface marker was used for quantification of activated basophils. RESULTS: With higher concentrations of histamine, we observed inhibition on optimally anti-IgE-stimulated basophil activation with a clear concentration dependency. With low concentrations of histamine (up to 10(-31)), we also observed inhibition of IgE-mediated basophil activation. Differences were observed between the dilution media. CONCLUSION: The preliminary results support the hypothesis that the dilution medium may influence the effects of high dilutions. This could be of importance for homeopathic pharmaceutical practice as well as for ultra-high dilution experiments. The refined basophil test system proved to be highly sensitive and reliable. Further studies are needed.

Antibodies, Anti-Idiotypic↗
PubMed2000

The relationship between serum IgE and surface levels of FcepsilonR on human leukocytes in various diseases: correlation of expression with FcepsilonRI on basophils but not on monocytes or eosinophils.

BACKGROUND: Expression of receptors for IgE (FcepsilonR) have been mainly studied on mast cells and blood basophils in the context of allergic disease. Some reports have noted limited expression of FcepsilonR on other leukocytes, including blood monocytes and eosinophils in certain patients. An association between human blood basophil expression of FcepsilonRIalpha and serum IgE has been noted among allergic subjects. OBJECTIVE: Recent evidence supports regulation of FcepsilonRIalpha by free IgE on both mast cells and basophils. We hypothesized that this relationship would exist across an extremely wide range of IgE levels for human basophils, irrespective of underlying disease. We further examined whether a similar relationship existed between serum IgE and FcepsilonRIalpha or FcepsilonRII (CD23) expression on monocytes and eosinophils in these same subjects. METHODS: Blood was obtained from nonallergic subjects (n = 3) and subjects with allergic asthma (n = 5), atopic dermatitis (n = 3), hypereosinophilic syndromes (n = 7), hyper-IgE syndrome (n = 6), helminth infestation (n = 6), or IgE myeloma (n = 1). Levels of serum IgE were determined by using RIA and ranged from 3 to 4.7 mg/mL. Levels of cell surface FcepsilonRIalpha, FcepsilonRII, and IgE were measured by using immunofluorescence and flow cytometry. RESULTS: Basophil surface IgE density and FcepsilonRIalpha expression correlated with serum IgE levels (r = 0. 67 and r = 0.46, respectively; P <.01; n = 31) regardless of the disease state. In contrast, monocyte FcepsilonRIalpha expression did not correlate with serum IgE (r = 0.09, P >.5, n = 29), and low-level eosinophil FcepsilonRIalpha expression was only detected in a single asthmatic subject. CD23 expression was not detected on basophils or eosinophils, except for the eosinophils from the donor with IgE myeloma. CD23 was present on monocytes from some donors but did not correlate with serum IgE levels. CONCLUSIONS: In a variety of disease states, FcepsilonRIalpha expression by basophils, but not monocytes or eosinophils, correlated with serum IgE levels across a 6-log range of IgE. These data support the concept of in vivo regulation of FcepsilonRIalpha on basophils by serum IgE and further demonstrate that this is independent of allergic disease per se.

Adolescent↗
PubMed2002

Proteasome-dependent regulation of Syk tyrosine kinase levels in human basophils.

BACKGROUND: In human basophils, FcepsilonRI signal initiation, leading to histamine release, relies on activation of Syk protein tyrosine kinase. Basophils from approximately 10% of unselected donors do not degranulate in response to FcepsilonRI cross-linking. Their unresponsiveness has been linked to the absence of Syk protein despite apparently normal levels of Syk mRNA. OBJECTIVE: The aim of this study was to explore pathways of Syk protein degradation as a possible posttranslational mechanism for downregulating Syk protein levels in human basophils and other leukocytes. METHODS: Highly purified basophils, lymphocytes, and monocytes were incubated in the presence or absence of a panel of cell-permeable inhibitors of proteolytic degradation pathway(s). Subsequently, the protein level of Syk tyrosine kinase was determined by means of Western blotting. In vitro assays were conducted through use of immunoprecipitated basophil Syk and a rabbit reticulocyte lysate system. RESULTS: Three inhibitors of proteasome-mediated degradation-PSI, lactacystin, and ALLN-substantially increased Syk levels in releaser basophils and restored Syk expression in nonreleaser basophils. Caspase inhibitors were less effective, and inhibitors of calpain-mediated proteolysis had no effect. Among other leukocytes tested, only naive CD4(+) T cells had more Syk after proteasome inhibitor treatment. In vitro ubiquitination assays demonstrated that Syk is readily ubiquitinated in vitro and also that Syk ubiquitination is associated with a substantial decrease in total levels of Syk protein. CONCLUSION: These data provide evidence for a ubiquitin/proteasome-dependent mechanism that contributes to Syk regulation in human basophils and might also be relevant to naive T cells. Understanding this regulatory pathway might lead to strategies for suppressing allergic inflammation while preserving essential Syk-mediated functions in other hematopoietic cells.

Basophils↗
PubMed2003

Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils.

BACKGROUND: Activation of mast cells and basophils through allergen stimulation releases chemical mediators and synthesizes cytokines. Among these cytokines, IL-4, IL-13, and IL-5 have major roles in allergic inflammation. OBJECTIVE: We sought to determine the potency of flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) for the inhibition of cytokine expression and synthesis by human basophils. METHODS: The inhibitory effect of flavonoids on cytokine expression by stimulated KU812 cells, a human basophilic cell line, and freshly purified peripheral blood basophils was measured by means of semiquantitative RT-PCR and ELISA assays. The effects of flavonoids on transcriptional activation of the nuclear factor of activated T cells were assessed by means of electrophoretic mobility shift assays. RESULTS: Fisetin suppressed the induction of IL-4, IL-13, and IL-5 mRNA expression by A23187-stimulated KU812 cells and basophils in response to cross-linkage of the IgE receptor. Fisetin reduced IL-4, IL-13, and IL-5 synthesis (inhibitory concentration of 50% [IC(50)] = 19.4, 17.7, and 17.4 micromol/L, respectively) but not IL-6 and IL-8 production by KU812 cells. In addition, fisetin inhibited IL-4 and IL-13 synthesis by anti-IgE antibody-stimulated human basophils (IC(50) = 5.1 and 6.2 micromol/L, respectively) and IL-4 synthesis by allergen-stimulated basophils from allergic patients (IC(50) = 4.8 micromol/L). Among the flavonoids examined, kaempferol and quercetin showed substantial inhibitory activities in cytokine expression but less so than those of fisetin. Fisetin inhibited nuclear localization of nuclear factor of activated T cells c2 by A23187-stimulated KU812 cells. CONCLUSION: These results provide evidence of a novel activity of the flavonoid fisetin that suppresses the expression of T(H)2-type cytokines (IL-4, IL-13, and IL-5) by basophils.

Basophils↗
PubMed1989

Interleukin 3 activates human blood basophils via high-affinity binding sites.

Pure populations of human basophilic granulocytes were obtained from chronic myeloid leukemia (CML) blood by negative selection using a mixture of monoclonal antibodies and complement. 125I-radiolabeled recombinant human interleukin 3 (rhIL-3) bound to purified basophils in a specific manner. Quantitative binding studies and Scatchard plot analyses performed on samples from two donors revealed the presence of a single class of high-affinity IL-3 binding sites (500 and 2100 sites per cell; dissociation constant at equilibrium, 230 and 160 pmol/liter, respectively). Purified CML basophils maintained in suspension in the presence of rhIL-3 (100 units/ml) incorporated up to 12 times more [3H]thymidine than basophils in control cultures. Furthermore, after preincubation in vitro with rhIL-3 (100 units/ml) for 30 min, normal blood basophils released 2- to 3-fold more histamine than basophils pretreated with control medium when exposed to various concentrations of an anti-IgE antibody. Together, these results show that rhIL-3 binds to a specific receptor on blood basophils and is a regulator of basophil function.

Antibodies, Monoclonal↗
PubMed1972

Basophilic leukocytes in allergic contact dermatitis.

A variety of cell-mediated hypersensitivity reactions in experimental animals include a prominent infiltrate of basophilic leukocytes. This form of reactivity has been designated cutaneous basophil hypersensitivity and is favored when sensitization to several types of antigen is accomplished without the use of complete Freund's adjuvant. A similar type of hypersensitivity response was sought in man using morphologic techniques which permit identification of basophilic leukocytes. Eight individuals with allergic contact dermatitis to a variety of allergens were studied and six of these developed typical contact reactions with erythema, edema, and epidermal vesicles. The microscopic findings in 3-day biopsies from these individuals differed significantly from classic descriptions of tuberculin hypersensitivity and showed, in addition to mononuclear cells and the characteristic epidermal changes, a substantial infiltrate of basophilic leukocytes and evidence of altered vascular permeability with vascular compaction, dermal edema, and fibrin deposition. Serial biopsies from one individual permitted analysis of the microscopic pathology as it unfolded at successive intervals after patch test. The initial lesion consisted of perivascular accumulations of lymphocytes; this was followed by an influx of basophils and, subsequently, of eosinophils. These findings associate contact allergy in man with the parallel reactions of cutaneous basophil hypersensitivity in animals and provide further evidence for the heterogeneity of the cellular immune response. The data are consistent with the hypothesis that interaction between sensitized lymphocytes and antigen, at a local test site, is responsible for the attraction of basophils. They also directly implicate the clotting system in delayed-type reactions and suggest the possibility of a synergistic relationship between cellular immunity and reactions mediated by basophil-bound, homocytotrophic antibody.

Adult↗
PubMed1994

Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine.

CC chemokines constitute a novel class of cytokines that attract and activate monocytes and lymphocytes, as well as basophil and eosinophil leukocytes, with distinct target cell profiles, and are believed to be involved in the regulation of different types of inflammation. The action of the recently identified monocyte chemotactic protein 3 (MCP-3) on human basophil and eosinophil function was studied and compared with that of other CC chemokines. In basophils, MCP-3, MCP-1, RANTES, and macrophage inflammatory protein (MIP)-1 alpha all induced cytosolic-free calcium concentration ([Ca2+]i) changes and, with different efficacies, chemotaxis (RANTES = MCP-3 >> MCP-1 > MIP-1 alpha), histamine release (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha), and leukotriene C4 formation, after IL-3 pretreatment (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha). Thus, MCP-3 was as effective as MCP-1 as an inducer of mediator release, and as effective as RANTES as a stimulus of basophil migration. In contrast to MCP-1, MCP-3 was also a stimulus for eosinophils, and induced [Ca2+]i changes and chemotaxis as effectively as RANTES, which is the most potent chemotactic cytokine for these cells. Desensitization of the transient changes in [Ca2+]i was used to assess receptor usage. In basophils, stimulation with MCP-3 prevented responsiveness to MCP-1 and RANTES, but not to MIP-1 alpha. No single CC chemokine (except for MCP-3 itself) affected the response to MCP-3, however, which was prevented only when the cells were prestimulated with both MCP-1 and RANTES. In eosinophils, by contrast, cross-desensitization between RANTES and MCP-3 was obtained. RANTES and to a lesser extent MCP-3 also desensitized eosinophils toward MIP-1 alpha. The desensitization data suggest the existence of three chemokine receptors: (a) a MCP-1 receptor expressed on basophils but not eosinophils that is activated by MCP-1 and MCP-3; (b) a RANTES receptor in basophils and eosinophils that is activated by RANTES and MCP-3; and (c) a MIP-1 alpha receptor that is activated by MIP-1 alpha, RANTES and, more weakly, by MCP-3. This study shows that MCP-3 combines the properties of RANTES, a powerful chemoattractant, and MCP-1, a highly effective stimulus of mediator release, and thus has a particularly broad range of activities toward both human basophil and eosinophil leukocytes.

Basophils↗
PubMed2004

Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite.

Using mice in which the eGfp gene replaced the first exon of the Il4 gene (G4 mice), we examined production of interleukin (IL)-4 during infection by the intestinal nematode Nippostrongylus brasiliensis (Nb). Nb infection induced green fluorescent protein (GFP)pos cells that were FcepsilonRIpos, CD49bbright, c-kitneg, and Gr1neg. These cells had lobulated nuclei and granules characteristic of basophils. They were found mainly in the liver and lung, to a lesser degree in the spleen, but not in the lymph nodes. Although some liver basophils from naive mice express GFP, Nb infection enhanced GFP expression and increased the number of tissue basophils. Similar basophil GFP expression was found in infected Stat6-/- mice. Basophils did not increase in number in infected Rag2-/- mice; Rag2-/- mice reconstituted with CD4 T cells allowed significant basophil accumulation, indicating that CD4 T cells can direct both tissue migration of basophils and enhanced IL-4 production. IL-4 production was immunoglobulin independent and only partially dependent on IL-3. Thus, infection with a parasite that induces a "Th2-type response" resulted in accumulation of tissue basophils, and these cells, stimulated by a non-FcR cross-linking mechanism, are a principal source of in vivo IL-4 production.

Animals↗
PubMed2006

Evaluation of basophil activation in food allergy: present and future applications.

PURPOSE OF REVIEW: The diagnosis of immediate hypersensitivity relies on specific IgE and history. Because of low specificity, however, provocation challenges are often necessary. Furthermore, IgE testing does not predict features such as reaction severity; nor can it discriminate cross-reactivity from multiple sensitizations. Direct and passive basophil activation tests may address these needs. In addition, measuring basophil activation ex vivo may be useful for monitoring patients with food allergies. RECENT FINDINGS: Several papers using basophil activation tests demonstrate comparable sensitivity and specificity to current testing for food allergy. Flow-based basophil activation tests have also been used to assess functional characteristics of patient IgE. Finally, several activation phenotypes have been identified as markers of allergic inflammation in vivo; these phenotypes appear to correspond to earlier reports of spontaneous histamine-releasing basophils in patients with active allergic inflammation. SUMMARY: Although in their early stages, direct basophil activation tests may prove to be useful in the clinic. Indirect basophil activation studies are useful when applied to compare functional aspects of IgE. Identification of basophil activation ex vivo is a promising approach for monitoring allergic inflammation.

Antigens, CD↗