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PubMed1978

The role of basophils in inflammatory reactions.

This review demonstrates that basophils reflect skin and lung mast cell reactivity and show characteristic changes in mediator release associated with clinical disease. Although the numbers of IgE molecules and IgE receptors on basophils have been enumerated, these have, in most instances, little influence on the release of histamine after challenge. There is, rather, a parameter of "releasability" that may be a major variable in allergic disease states. Basophils contain and release histamine, the eosinophil chemotactic factor of anaphylaxis (ECFA), a slow reacting substance of anaphylaxis (SRS-A), and a kallikrein. The release process is controlled by hormone-basophil receptor interactions that determine the cyclic AMP level; plasma and tissue adenosine levels appear prominent in this control. Histamine feeds back to negatively modulate basophil and mast cell release through a specific histamine 2-receptor; it also inhibits lymphocyte and neutrophil function. Like neutrophils, basophils contain beta-glucuronidase while neutrophils contain SRS-A and a low-molecular-weight ECF. The stimuli for primary basophil and neutrophil release are, however, quite different, although phagocytic stimuli, which fail to cause basophil mediator release, potentiate the IgE response. It is concluded that basophols play a significant in vivo role in inflammation by acting as an interface between foreign antigens, the serum cascade systems, and other inflammatory cells.

Antigen-Antibody Reactions↗
PubMed1987

The purification of human basophils: their immunophenotype and cytochemistry.

An IgM class monoclonal antibody Bsp-1 that selectively reacts with human basophils was used to label basophils in normal and leukaemic haemopoietic samples. The immunophenotype of Bsp-1+ basophils was determined using a panel of 21 IgG subclass monoclonal antibodies in two-colour immunofluorescence assays. Basophils expressed the leucocyte common antigen, HLA-ABC antigens and antigens defined by CD11 and CD13 monoclonal antibodies. Other myeloid cell (granulocyte-monocyte) associated anti-antigens, lymphoid cell surface determinants and HLA-DR antigens were not detected. Basophil preparations of 95-98% purity were obtained from the peripheral blood of patients with CML and umbilical cords using fluorescence activated cell sorting techniques. Purified basophils exhibited metachromatic staining with toluidine blue, alcain blue and astra blue. PAS staining was observed in 7% of cord Bsp-1+ cells and of 55% CML Bsp-1+ cells. Between 5% and 10% of basophils were chloroacetate esterase-positive which suggests that some Bsp-1+ cells are immature basophils.

Antibodies, Monoclonal↗
PubMed1981

Differences in response to anti-IgE and to anti-IgG in basophils from patients with bronchial asthma.

Peripheral blood basophils of thirty-eight patients with bronchial asthma were examined for their reactivity to anti-IgE and anti-IgG antisera. Basophils of patients with serum IgE levels of more than 1001 i.u./ml reacted strongly to anti-IgE. Basophils of patients with serum IgE levels of less than 100 i.u./ml had a tendency to react more strongly to anti-IgG. An index (basophil ratio) was devised to compare the patient basophil reactivity to anti-IgE and anti-IgG. This basophil ratio was lower (IgE dominant) in the atopic cases which usually exhibited a high serum IgE level. Most cases with low serum IgE exhibited a high basophil ratio (IgG dominant). The basophils of seven intractable patients reacted more strongly to anti-IgG than to anti-IgE regardless of the serum IgE level.

Antibodies, Anti-Idiotypic↗
PubMed1985

Basophil immunoglobulin receptors in asthmatics under immunoscanning electron microscopy.

Immunolatex particles were used as markers for IgE receptors on basophils using electron-microscope scanning. These particles appeared to bind specifically to basophils. Basophils from atopic asthma patients showed greater binding to latex particles than those from intractable asthma patients or healthy subjects. Cap and patch formations on IgE receptors were frequently found in basophils of atopic asthmatics, and cap formation was observed only on basophils that were pear-shaped. The redistribution of IgE receptors, such as that by cap formation, may be a significant triggering mechanism for basophil activation. The latex density on basophils pre-treated with anti-human IgG was much greater in intractable asthmatics than in atopic asthmatics or healthy subjects, and almost all basophils with increased immunolatex particles were pear-shaped, suggesting the presence of some IgG receptors on the surface, and such receptors may play an important role in intractable asthma.

Asthma↗
PubMed1977

Quantitative and qualitative estimations of IgE bound to basophil leukocytes from hay fever patients.

IgE was removed from human basophils of 4 nonatopic persons and 10 hay fever patients allergic to timothy grass pollen by treating the cells with buffer adjusted to pH 4. IgE could be removed and refixed to the same cells. Refixation was demonstrated by immunofluorescence and by the ability of basophils to release histamine on exposure to timothy pollen. Removed total IgE and specific IgE directed against timothy pollen were estimated, and a linear correlation to the level of total IgE and specific IgE in serum was found. The total number of IgE molecules per basophil was calculated to be in the range of 30,000 to 300,000, and timothy-specific IgE constituted 4%-15% of the total IgE molecules on the cells. It was furthermore established that specific cell-bound IgE was linearly correlated to the pollen concentration releasing 20% of the histamine contents of the basophils. Separated 2gE from sensitized and nonsensitized basophils could be bound to basophils from other patients, resulting in a change in cell sensitivity. This could be ascribed to additional binding to free cell receptors as well as to a partial replacement of bound IgE. Basophils from non-atopic persons could not be sensitized by incubation with surface IgE from atopic persons. The results indicate that acid treatment is a simple method suitable for removing IgE from basophils. This IgE is intact and can be quantitated.

Adult↗
PubMed1990

Passive sensitization and histamine release of basophils. IgE and cellular factors regulating histamine release.

This study had two purposes. First, to examine a possible functional heterogeneity of IgE regulating basophil histamine release and the effect of using two different donor cells for passive sensitization experiments. Second, to investigate basophils not releasing histamine to anti-IgE by stimulating protein kinase C with the addition of the phorbol-ester, TPA. In consecutive experiments responding donor basophils were passively sensitized with plasma from non-responding subjects. Thus, the first set of experiments included passive sensitization of acid treated donor basophils from one atopic and one non-atopic patient with plasma from 29 children with exogenous asthma to grass pollen, cat dander, or dust mites. Different secretagogues (anti-IgE, Concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine) induced different histamine release responses due to a cellular property of the basophils not related to the type of IgE bound to the cell membrane. It was demonstrated that the allergen-induced histamine release did not depend on the extract or type of IgE when the biological activity of each extract and serum-specific IgE levels were similar. However, the atopic donor cells released significantly (P less than 0.05) more histamine than non-atopic donor cells. Thus, histamine release depends on the type of secretagogues and a cellular property which is maybe influenced by the presence of serum factors and a certain type of IgE in the serum of atopics. The second set of experiments included 10 patients (6 atopics and 4 non-atopics) with non-histamine releasing basophils. In the presence of 10 ng/ml TPA, however, seven of 10 patients released histamine at anti-IgE challenge. Three months later two additional patients became responsive in the presence of TPA. By passive sensitization of responding donor basophils the non-responding patients were shown to possess functionally intact IgE. Thus, the discrepancies sometimes observed between clinical symptoms, serological IgE-antibody measurements and histamine release testing in allergic patients may be related to a cellular property of basophils.

Adolescent↗
PubMed1998

Unstimulated basophils in atopic and nonatopic subjects express intracellular interleukin-4: detection by flow cytometry.

BACKGROUND: IgE-stimulated cultured basophils from atopic subjects are capable of secreting interleukin-4 (IL-4). We describe a flow-cytometric technique which identified intracellular IL-4 in unstimulated basophils unseparated from peripheral blood mononuclear cells (PBMC) in both atopic (AT) and nonatopic (NC) volunteers. METHODS: Freshly isolated PBMC were fixed in 4% paraformaldehyde (PFA). Surface staining with 22E7, a noncompetitive anti-FcepsilonRI-alpha antibody, allowed identification of basophils. Permeabilization by 0.1% saponin allowed staining of intracellular cytokines with specific monoclonal antibodies (mAbs). Two series of experiments utilizing different protocols and anticytokine mAbs were performed. The first protocol required a two-stage fluorochrome staining technique. The availability of fluorochrome-conjugated mAbs allowed a simpler, one-stage labelling procedure for the second protocol. RESULTS: With the first protocol, IL-4 (but not IFN-gamma), immunoreactivity was detectable in a majority (median 77%) of peripheral blood basophils from both AT and NC subjects (n=8). Basophil IL-4 immunoreactivity was again evident in experiment 2 but did not differ significantly between AT and NC subjects--either evaluated as percentage of IL-4+ basophils (AT median=66%, NC median=38.4%, P=0.41) or IL-4-specific mean fluorescence (AT median=0.85, NC median=0.3, P=0.07). CONCLUSIONS: This simple technique allowed the study of intracellular cytokine expression in unstimulated blood basophils. It demonstrated constitutive basophil expression of IL-4 (but not IFN-gamma) in all subjects, with no significant increases in atopics.

Adult↗
PubMed1996

Regulation of human basophil function by phosphatase inhibitors.

1. Okadaic acid, a cell permeant inhibitor of protein serine/threonine phosphatases (PPs), attenuated the IgE-mediated release of the pre-formed mediator, histamine from human basophils in a time- and dose-dependent manner. Optimal inhibition (77 +/- 4%, P < 0.0001) of histamine release was observed following a 2 h incubation with 1 microM okadaic acid. 2. Okadaic acid and two analogues of okadaic acid were also studied and were found to inhibit the IgE-dependent release of histamine. Concentrations required to inhibit release by 50% (IC50) were 0.6 microM for okadaic acid and 7.5 microM for okadaol, whereas okadaone was inactive. 3. The structurally-unrelated PP inhibitor, calyculin A, also inhibited IgE-dependent histamine release from basophils dose-dependently and was approximately six fold more potent than okadaic acid. 4. The IgE-mediated generation of sulphopeptidoleukotrienes (sLT) from basophils was inhibited by okadaic acid and related analogues with the following rank order of potency; okadaic acid (approx. IC50 0.3 microM) > okadaol (3 microM) > okadaone (inactive). 5. Okadaic acid, okadaol and okadaone (all at 3 microM) inhibited the IgE-mediated generation of the cytokine interleukin 4 (IL4) from human basophils by 67 +/- 9% (P < 0.002), 48 +/- 14% (P < 0.05) and 8 +/- 7% (P = 0.31), respectively. 6. Extracts of purified human basophils liberated 32P from radiolabelled glycogen phosphorylase and this PP activity was inhibited by 17 +/- 3% (P < 0.0005) by a low (2 nM) concentration of okadaic acid and was inhibited by 96 +/- 1% (P < 0.0001) by a higher (5 microM) concentration of okadaic acid. Because a low (2 nM) concentration of okadaic acid inhibits PP2A selectively whereas a higher (5 microM) concentration inhibits both PP1 and PP2A, these findings suggest that both PP1 and PP2A are present in basophils. 7. In total these data suggest that PPs are resident in human basophils and that PPs may be important in the regulation of basophil function.

Basophils↗
PubMed2006

Basophils, basophilia and helminth infections.

A growing body of evidence suggests basophils are important components of the human immune response to helminth infections. Basophil numbers are increased in several animal models of helminth infection, and basophils have been shown to release both histamine and IL-4 in response to helminths. Helminth infections typically provoke type 2 immune responses characterized by eosinophilia, elevated levels of Ag-specific and polyclonal IgE, and T cell production of type 2 cytokines such as IL-4, IL-5, and IL-13. IL-4 plays a central role in this type 2 response. As basophils are the only peripheral blood mononuclear cells with the ability to release IL-4 rapidly in response to appropriate stimuli, releasing large quantities of preformed IL-4 within minutes of surface IgE cross-linking, it appears likely that basophils play an important role in amplifying ongoing type 2 immune responses to helminth infections once Ag-specific IgE is present. Basophils may also function to initiate type 2 responses upon first exposure to helminths and to potentially re-establish these responses upon re-exposure. This article reviews basic basophil biology and physiology, evaluates the evidence for the presence of basophilia in helminth infections, and then focuses on the possible roles basophils serve in the immune response to helminth infections.

Allergens↗
PubMed2006

Diagnostic tests based on human basophils: potentials, pitfalls and perspectives.

Human basophils are important tools for studying immediate-type hypersensitivity reactions since they release a variety of mediators (e.g., histamine, leukotriene C4, IL-4 and IL-13) following allergen triggering. Several diagnostic tools have been introduced that measure either leukotriene production or the upregulation of surface markers (CD63 and CD203c) from these cells after antigen stimulation. However, a broad variability in basophil activity exists between different basophil donors and different antigens within one donor. This manifests itself in terms of their reactivity (maximum secretory response), based on the intracellular signaling of the basophils studied, and in terms of their sensitivity. The latter is governed by the number of IgE receptors per basophil, the ratio of antigen-specific IgE to total IgE, and by the number of cell surface antigen-specific IgE molecules for half-maximal responses, termed 'intrinsic sensitivity'. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests for diagnostic purposes, each allergen should be pre-evaluated separately in order to determine a suitable stimulation range. Additionally, anti-IgE or anti-FcepsilonRIalpha antibodies should serve as positive controls, bearing in mind that 10-20% of basophil donors are not responsive to IgE-mediated stimulation. Diagnostic studies using CD63 or CD203c in hymenoptera, food and drug allergy are critically discussed. Basophil-based tests are indicated for allergy testing in selected cases but should only be performed by experienced laboratories.

Animals↗
PubMed2006

Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy.

BACKGROUND: Studies using rush immunotherapy (RIT) have shown that rapid protection can be achieved using protocols allowing a fast increment of allergen dose. We examined the early effects of RIT on basophil numbers and expression of CD203c, production of interleukin (IL)-4 and IL-13 and histamine release by basophils in the peripheral blood of patients treated with immunotherapy and controls. METHODS: Twelve patients treated with RIT and 4 untreated controls were included in the study. Any adverse events were evaluated during the incremental phase of RIT. Mononuclear cells were isolated before the start of RIT and 3 days, 1 week, 4 weeks and 3 months after the beginning of the treatment. Histamine release upon allergen stimulation, expression of CD203c and allergen-induced production of IL-4 and IL-13 by basophils were examined. RESULTS: Significant decreases in blood basophil count (p = 0.02) were observed early in the treatment, returning to baseline values 1 week after the start of RIT. Similarly, histamine release decreased at day 3 (p = 0.02), but returned to pretreatment levels after 1 week. Also, the percentage of IL-4+ and IL-13+ basophils and levels of CD203c expression were markedly reduced early in the treatment. IL-4 and IL-13 production correlated with histamine release and CD203c expression. Histamine release and production of IL-4 and IL-13 by basophils before the treatment correlated with the severity of adverse events during the incremental phase of RIT. CONCLUSION: We report the decrease in blood basophil numbers, their lower activation status and the reduced production of IL-4 and IL-13 early in the course of RIT. This early suppression of basophil activation could be one mechanism behind the protective effect of RIT.

Adult↗
PubMed1981

A new look at basophils in mice.

It is believed that mice do not express cutaneous basophil hypersensitivity because they have few or no basophils. We have looked for these cells in peripheral blood smears of C3H/He, DBA/2, C57BL/6, and Balb/c mice before and after a series of foreign protein injections, a treatment known to induce basophilia. We found 0.2 and 1.5% basophils in the untreated C3H/He and DBA/2 mice and no basophils in the untreated C57BL/6 and Balb/c mice. Basophilia of 2--10% was found in the treated mice of the four strains. We noticed that the microscopic appearance of the mouse basophils differs from that in other species. These results indicate that basophils may be as frequent in mice--believed not to express cutaneous basophil hypersensitivity--as they are both in man and guinea pigs--known to express this entity. Since the mouse basophils have a distinct morphology, different from that of other species, it is possible that they may not have been noticed in routine skin preparations.

Animals↗
PubMed1991

Regulation of mediator release by human basophils: importance of the sequence and time of addition in the combined action of different agonists.

Biologically active molecules affecting basophil function can be divided into 4 groups according to their capacity to induce basophil degranulation and/or leukotriene generation: (1) full agonists such as anti-IgE or fMLP, which induce both histamine and leukotriene release; (2) partial agonists such as C5a, which induces degranulation only; (3) incomplete agonists such as neutrophil-activating peptide-1, platelet-activating factor or C3a, which induce mediator release only after cytokine preincubation, and (4) basophil response modifiers, such as interleukin-3, interleukin-5 and granulocyte/macrophage- colony-stimulating factor, which (a) enhance the releasability to all basophil agonists, (b) change the mediator profile, (c) enhance the rate of mediator release, (d) render basophils responsive to lower agonist concentrations and (e) render basophils responsive to incomplete agonists. We demonstrated that histamine release and de novo synthesis of lipid mediators are clearly separately regulated, and that combined actions of different molecules are of importance. In particular, the type(s), the time interval and the sequence of action of basophil-activating molecules are crucial for the final outcome of the basophil release reaction.

Basophils↗
PubMed1997

Molecular and cellular biology of mast cells and basophils.

In all mammalian species investigated so far, mast cells and basophils are the only cells that synthesize histamine and express plasma membrane receptors that bind IgE with high affinity (Fc epsilonRI). Human basophils and mast cells derive from distinct precursors that originate in the bone marrow and fetal liver and probably circulate in peripheral blood. There is extensive evidence that mast cells and basophils and their mediators are primary effectors of allergic inflammation. Immunologically activated human basophils release two cytokines: IL-4 and IL-13. Expression of several cytokines has been documented in a number of experimental models of human and rodent mast cells. However, to date few studies have analyzed the mechanisms of gene expression in human Fc epsilonRI+ cells. Some of these studies imply a role for NFAT and GATA family members in the IgE-mediated activation of cytokine gene transcription in basophils and mast cells. Studies of human basophils and mast cells isolated from different anatomic sites have established the different profiles of eicosanoids released by these cells. Recently, the characterization of arachidonic acid pools and the identification of novel enzymes involved in arachidonate remodeling and mobilization clarified in part how eicosanoid productions is regulated in mast cells and basophils. In addition to histamine, human mast cell secretory granules contain the neutral proteases tryptase, chymase and carboxypeptidase that possess several biochemical properties. In particular, tryptase may play a role as a fibrogenic factor and chymase might convert angiotensin I to angiotensin II. Mast cells are present in human heart and in human coronary arteries raising the possibility that local activation of cardiac mast cells might contribute to certain cardiovascular diseases. Recent evidence also suggests that mast cells and basophils can play a role during viral and bacterial infections. It is now evident that in man these two cells not only participate in inflammation associated with allergic disease, but also in chronic and fibrotic disorders affecting several organs and in host defense against bacterial and viral infections.

Animals↗
PubMed2001

Immunohistochemical detection of human basophils in postmortem cases of fatal asthma.

The role of human basophils in bronchial asthma has been hard to define. In this study, we used the basophil-specific monoclonal antibody (mAb), 2D7, in postmortem lung sections from individuals who die in status asthmaticus (fatal asthma [FA]) to determine if the pathology of FA is associated with an increase in basophil numbers in the lung. As controls, we used lung sections of patients who had a history of asthma but died from nonasthmatic causes (nonfatal asthma [NFA]) as well as patients with no history of asthma (control [C]). In lung sections from all three groups, basophils were scattered throughout the large and small airways, airway epithelium, submucosa, and alveolar walls. The numbers of basophils in the lungs of patients with FA ranged from 41 to 119 cells/mm(2), significantly more than the numbers of basophils in lungs from individuals with a history of asthma (NFA; 0 to 16 cells/ mm(2)) and in the control lungs (C; 0 to 13 cells/mm(2)). In contrast, CD45-positive cells were not significantly different in the airways of FA and NFA, although there were significant increases in the two groups compared with control subjects. In summary, basophil infiltration was significantly increased in lungs from individuals who died from asthma, supporting the hypothesis that basophils are involved in the pathogenesis of FA.

Adolescent↗
PubMed1983

Ultrastructural criteria for identification of mast cells and basophils in humans, guinea pigs, and mice.

Basophils and mast cells represent distinct populations that may express differences in function, biochemistry, and response to drugs. In this review, we define ultrastructural criteria useful in distinguishing basophils from mast cells in humans, the guinea pig, and the mouse. Although the ultrastructural features of normal mature basophils and mast cells are the main subject of this report, we also describe variations in basophil and mast cell ultrastructure that reflect the cells' functional activity or stage of maturation. Appreciation of such ultrastructural changes, which can strikingly alter the appearance of these cells, is particularly important in identifying basophils and mast cells in sites of inflammation. In addition to facilitating the accurate identification of basophils and mast cells in vivo, ultrastructural analysis has played an important role in in vitro studies of basophil and mast cell maturation and function. The morphology and biochemistry of these cells now can be studied either by analyzing highly purified populations derived from blood or tissues, notably the lung, or by examining cloned cell lines maintained in vitro. Exploitation of these important technical advances promises to rapidly increase our understanding of the roles of basophils and mast cells in health and disease.

Animals↗
PubMed1986

Enhanced IgE-dependent basophil histamine release and airway reactivity in asthma.

IgE-dependent basophil histamine release does not necessarily correlate with the amount of cell-bound IgE, thus it has been suggested that basophil "releasability" is an important, but yet undefined, factor in this secretory process. Because mast cell, and possibly basophilic leukocyte, mediator release contributes to airway reactivity, any enhancement of this secretory process would favor asthma provocation. To evaluate IgE-dependent basophil histamine releasability in asthma, suspensions of leukocytes were isolated from patients with an allergic and nonallergic component to their airway disease and stimulated with concanavalin A (Con A) (0.03 to 10.0 micrograms/ml) and anti-IgE (10 to 1,000 ng/ml). Basophil histamine release to Con A and anti-IgE was significantly greater in both allergic and nonallergic asthmatic patients when compared with normal subjects. In contrast, basophil histamine release to the calcium ionophore A23187 was similar in leukocytes from normal subjects and asthmatic patients, suggesting the observed abnormality in secretion may be limited to an IgE-dependent process. To further determine if basophil histamine releasability in asthma correlated to measures of airway reactivity, bronchial provocation with histamine was performed. An inverse correlation was found between the provocative dose of inhaled histamine required to produce a 20% decrease, PD20, in the FEV1 and the leukocyte histamine release to Con A (p less than 0.05) and anti-IgE (p less than 0.05). Thus, we have new evidence that enhanced IgE-dependent release of leukocyte histamine correlates with airway reactivity in asthma. The mechanism of basophil releasability and its relationship to the pathogenesis of airway reactivity in asthma have yet to be established.

Adult↗
PubMed1996

Effects of integrin clustering on human lung mast cells and basophils.

The interaction of cells with the extracellular matrix can alter cell responses and is regulated by integrins on the cell surface. We used monoclonal antibodies to the VLA-4 integrins CD29 and CD49d followed by an F(ab')2 fragment of rabbit anti-mouse immunoglobulin G1 to crosslink integrins on the surface of human lung mast cells and basophils. Crosslinking either CD29 or CD49d caused a significant histamine release (HR) from the basophils of most asthmatic donors (10 of 14 for CD49d and 7 of 10 for CD29) (HR = 21 +/- 5%, n = 10, P < 0.005 for CD29 and HR = 19 +/- 4%, n = 14, P < 0.01 for CD49d) yet failed to initiate HR from the basophils of non-atopic and atopic donors (HR was 1 +/- 0.5% for CD29 and 1 +/- 0.5% for CD49d, n = 10, P = NS). Crosslinking either CD29 or CD49d also failed to initiate histamine release from human lung mast cells (HR was 1 +/- 1% for CD29 and 2 +/- 1% for CD49d). The basophils of asthmatic donors responded to 100 and 30 micrograms/ml tissue fibronectin (HR = 12 +/- 2% and 10 +/- 3% for 100 and 30 micrograms/ml fibronectin, respectively, n = 18, P < 0.05), whereas basophils of nonasthmatic patients again failed to degranulate (HR was 0 +/- 0.4% and 1 +/- 0.6%, respectively, n = 11, P = NS). In contrast to the basophil, crosslinking of either CD29 or CD49d failed to initiate histamine release in human lung mast cells (HR = 1 +/- 1% for CD29 and 2 +/- 1%, n = 15). Human lung mast cells were also unresponsive to tissue fibronectin (100 and 30 micrograms/ml) (HR = 1 +/- 1%, n = 5). The tyrosine kinase inhibitor, genistein, significantly reduced CD29- and CD49d-induced HR (inhibition = 83 +/- 7% for CD29 and 77 +/- 6% for CD49d, n > or = 5, P < 0.05). A second tyrosine kinase inhibitor, piceatannol, also significantly reduced both CD29- and CD49d-induced HR (inhibition was 62 +/- 19% for CD29 and 56 +/- 14% for CD49d, n = 7, P < or = 0.05). Integrin crosslinking also affected the response to a second, immunoglobulin E (IgE)-dependent stimulus. Both CD29 and CD49d clustering significantly inhibited anti-IgE-induced histamine release from the human basophil. Inhibition was 30 +/- 5%, n = 18, P < or = 0.001 for CD29 versus 40 +/- 6% for CD49d. In summary, we have shown that crosslinking the beta 1 integrins using either monoclonal antibodies or tissue fibronectin can initiate mediator release from the basophils of asthmatic patients by a mechanism which appears to be tyrosine kinase-mediated. In addition, clustering of integrins modulates the response to a second IgE-dependent signal.

Antibodies, Monoclonal↗