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PubMed2003

Comparative effects of basophil-directed growth factors.

IL-3, IL-5, and GM-CSF exert various overlapping functions in basophils. We investigated the receptor expression profiles and concentration-dependent effects of IL-3, IL-5, and GM-CSF on several basophil functions in comparison with their effects on eosinophils. The order of the receptor expression levels was IL-3Ralpha>IL-5Ralpha>GM-CSFRalpha in basophils and IL-5Ralpha>or=GM-CSFRalpha>IL-3Ralpha in eosinophils. Compared with eosinophils, basophils expressed a much higher level of IL-3Ralpha and similar levels of IL-5Ralpha and GM-CSFRalpha. The order of potency was IL-3>IL-5=GM-CSF for degranulation, survival, and CD11b expression in basophils, and IL-5=GM-CSF>or=IL-3 for survival and CD11b expression in eosinophils. However, IL-3 induced CD69 expression preferentially in basophils. Our results indicate that IL-3 is the most potent activator of human basophils, and that the rank order of potency of hemopoietic growth factors virtually corresponded to their receptor expression levels in both cell types.

Antigens, CD↗
PubMed1996

Cyclosporin H is a potent and selective competitive antagonist of human basophil activation by N-formyl-methionyl-leucyl-phenylalanine.

BACKGROUND: Cyclosporin A (CsA) binds with high affinity to cyclophilin, a critical step in the molecular mechanism of action of cyclosporins, where cyclosporin H (CsH) has extremely low affinity for cyclophilin. CsH differs from CsA by the substitution of the L-methyl valine at position 11 with it D-isomer. METHODS: We compared the effects of CsA and CsH on the release of performed (histamine) and de novo synthesized inflammatory mediators (peptide leukotriene C4) from peripheral blood basophils activated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). RESULTS: CsH (8 to 800 nmol/L) concentration-dependently inhibited histamine and leukotriene C4 release from purified and unpurified basophils activated by FMLP, whereas CsA (8 to 800 nmol/L) had little inhibitory effect on histamine release from basophils challenged with FMLP. Inhibition of histamine release from basophils challenged with FMLP was extremely rapid and was abolished by washing the cells (three times) before challenge. CsH (8 to 800 nmol/L) had no effect on the release of histamine caused by C5a, platelet activating factor, monocyte chemotactic activating factor, RANTES, IL-8, bryostatin 1, and phorbol myristate. Preincubation of basophils with granulocyte-macrophage colony-stimulating factor (30 and 100 pmol/L), but not IL-1 beta (30 and 100 ng/ml), concentration-dependently reversed the inhibitory effect of CsH on FMLP-induced histamine release. CsH competitively inhibited the effect of FMLP on histamine release from basophils. The dissociation constant (Kd) for the CsH-FMLP receptor complex was approximately 9 x 10(-8) mol/L, more than 10-fold lower than that (approximately equal to 1.3 x 10(-6) mol/L) of N-t-BOC-methionyl-L-leucyl-phenylalanine (BocMLP), a known formyl peptide receptor antagonist. CsH inhibited tritiated FMLP binding to human polymorphonuclear leukocytes with a concentration required to inhibit binding by 50% of approximately 5.4 x 10(-7) mol/L, whereas BocMLP was less potent with a concentration required to inhibit binding by 50% of approximately 9.1 x 10(-5) mol/L. Scatchard analysis revealed that the decreased tritiated FMLP binding caused by CsH was due to a decrease in the Bmax (0.22 +/- 0.04 nmol/L/5 x 10(6) cells vs 0.09 +/- 0.01 nmol/L/5 x 10(6) cells; p < 0.05), without a significant difference in the Kd (5.16 +/- 1.22 nmol/L vs 6.32 +/- 2.42 nmol/L; p = NS). CONCLUSION: CsH is a potent and selective inhibitor of mediator release from basophils induced by activation of the formyl peptide receptor; it acts by interfering with agonist binding to FMLP receptors.

Basophils↗
PubMed1998

Immunohistochemical detection of human basophils in late-phase skin reactions.

BACKGROUND: Human basophils are difficult to detect with classic histochemical stains at sites of allergic inflammation. The 2D7 anti-basophil monoclonal antibody was used to identify basophils in skin during the late-phase response to a cutaneous allergen challenge. METHODS: The 2D7 monoclonal antibody was used on protease-digested sections of skin biopsy specimens obtained 6 and 24 hours after an allergen or buffer challenge. The skin chamber technique was used to compare buffer- and allergen-challenged sites at 6 hours, and intradermal injection of allergen was used to compare allergen-challenged sites at 6 and 24 hours. RESULTS: Dramatic increases in the numbers of 2D7+ cells and in tissue staining by 2D7 were observed 6 hours after allergen challenge compared with buffer challenge. Histamine levels in skin chamber fluid varied with 2D7+ cell concentrations. By 24 hours, 2D7+ cells and tissue staining appeared to diminish but were still detectable in the allergen-challenged sites. Basophils localized primarily in and around blood vessels, whereas mast cells remained mostly in the superficial dermis. Mast cells were 2D7- in both the allergen- and buffer-challenged skin. Metachromatic staining of 2D7+ basophils with toluidine blue was absent in these tissue sections. CONCLUSIONS: The 2D7 monoclonal antibody provides a more sensitive and precise marker than histochemical staining for human basophil involvement during the late-phase response to an allergen challenge. Basophil infiltration was observed at 6 hours only after allergen challenge and persisted at similar levels by 24 hours.

Allergens↗
PubMed1999

Syk deficiency in nonreleaser basophils.

BACKGROUND: Peripheral blood basophils from 10% to 20% of donors fail to degranulate in response to cross-linking the high-affinity IgE receptor FcepsilonRI. The molecular mechanisms underlying the nonreleaser phenotype have not been established. OBJECTIVES: Our aim was to compare the expression of FcepsilonRI-associated protein tyrosine kinases between nonreleaser and releaser basophils. METHODS: With use of Western blotting we investigated Syk and Lyn protein levels in highly purified basophils from 3 anti-IgE nonreleasers and 2 releasers. RESULTS: We identified 3 healthy nonatopic donors whose nonreleaser basophils express FcepsilonRI normally but fail to express protein for the tyrosine kinase Syk, which is implicated in the initiation of FcepsilonRI-mediated secretion. Protein levels for the tyrosine kinase Lyn are somewhat reduced but not absent in nonreleaser basophils. Levels of Lyn and Syk protein are similar in B cells, eosinophils, and neutrophils from releaser and nonreleaser donors. During these studies one nonreleaser "converted" into a releaser with concomitant basophil Syk expression. CONCLUSION: The absence of detectable Syk could explain the nonreleaser phenotype of basophils from some donors.

Adolescent↗
PubMed2002

Difference in CD22 molecules in human B cells and basophils.

OBJECTIVE: CD22 is believed to be restricted to normal and neoplastic B cells. Human basophils were found to express CD22 molecules. Among the antibodies against CD22, Leu14, which recognized the ligand binding domain, reacted to basophils, and B3 and 4KB128, which recognized the amino terminus side and carboxy terminus side of the ligand binding epitope, respectively, did not. To clarify the difference of CD22 antigenicity in human B cells and basophils, we investigated RNA sequence and structures of CD22 molecules. MATERIALS AND METHODS: Purified B cells and basophils were obtained from normal human volunteers by using a MACS magnetic cell sorting system and anti-CD19 and anti-Fc epsilon R1 antibodies, respectively. RT-PCR and sequencing of CD22 mRNA were performed in the exons 3 to 8. Western blotting analysis of CD22 was also performed. RESULTS: The sequence of CD22 mRNA extracted from the basophils was the same as that of B cells in exons 3 to 8 (epitopes recognized by Leu14, B3, and 4KB128 were translated from exons 4 and 5). Reduced CD22 peptide extracted from the basophils reacted to Leu14 as well as B3 and 4KB128, and the molecular size of the reduced and nonreduced products was 130 kDa as expected. CONCLUSION: Disulfide bonds and the resulting 3D conformation of the CD22 molecules may have important roles in the difference of antigenicity of CD22 beta in B cells (CD22 beta 1) and basophils (CD22 beta 2). The difference in molecular structure surrounding the ligand-binding domain of CD22 may imply a specialization of the conformational forms of CD22 according to the ligand isoforms.

Adult↗
PubMed1998

Regulation of human mast cell and basophil function by cAMP.

1. Mast cells and basophils are important in mediating allergic disorders such as asthma. Activation of these cells results in the release of a wide variety of mediators that can promote inflammatory responses. 2. Receptor-mediated activators of adenylate cyclase such as the beta-adrenoceptor agonist, isoprenaline, and prostaglandin E2 (PGE2) are effective at inhibiting mediator release from human lung mast cells (HLMC) but not basophils. In HLMC, both isoprenaline and PGE2 elevate and sustain increases in cyclic adenosine 3',5'-monophosphate (cAMP) whereas in basophils, both compounds cause transient increases in cAMP. 3. Non-selective inhibitors of phosphodiesterase (PDE) such as theophylline and 3-isobutyl-1-methylxanthine are effective inhibitors of mediator release from both HLMC and basophils and both compounds cause elevations of cAMP that are sustained in both cell types. 4. Studies with selective inhibitors of PDE indicate that the cAMP-specific PDE, PDE 4, regulates the activity of basophils but not HLMC. The nature of the PDE regulating HLMC responses is uncertain. 5. These data indicate that agents that induce and sustain elevations in intracellular cAMP attenuate the stimulated release of mediators from mast cells and basophils. However, the responsiveness of HLMC and basophils to selected cAMP-active agents differs.

Adrenergic beta-2 Receptor Agonists↗
PubMed2003

IL3 effect on basophils histamine release upon stimulation with chronic urticaria sera.

BACKGROUND: Chronic urticaria is thought to be an autoimmune disorder in 35-40% of patients because of the presence of an immunoglobulin G (IgG) antibody reactive with the IgE receptor. Patients possessing this antibody are identified by the ability of serum to degranulate donor basophils to release histamine. We questioned whether priming of basophils with interleukin 3 (IL3) would facilitate identification of patients and/or alter the percentage of patients who have a positive assay. METHODS: We incubated 37 chronic urticaria sera with basophils from donors with no urticaria with and without priming with IL3 and compared histamine release in each instance. We also preincubated basophils from a 'non-releaser' with IL3, used these cells to assay chronic urticaria sera, and assessed the contribution of complement. RESULTS: Interleukin 3 increases the amount of histamine release by the sera which is able to activate basophils, but it does not convert negative sera into positive releasers. Interleukin 3 is able to partially reverse 'non-releaser' basophils into cells that respond to chronic urticaria sera, and complement cannot account for the augmentation seen. CONCLUSIONS: Preincubating basophils with IL3 facilitates the identification of sera with anti-IgE receptor antibody but does not affect the percentage of sera designated as positive.

Adult↗
PubMed2007

Role of calcineurin in the regulation of human lung mast cell and basophil function by cyclosporine and FK506.

BACKGROUND AND PURPOSE: Cyclosporine and FK506 are thought to act by targeting the Ca2+-dependent protein phosphatase, calcineurin. The aim of the present study was to determine whether cyclosporine and FK506 stabilize mast cells and basophils by interacting with calcineurin. EXPERIMENTAL APPROACH: The effects of cyclosporine and FK506 on the IgE-mediated release of histamine from mast cells and basophils were evaluated. The presence of calcineurin in cells was determined by Western blotting. Ca2+-dependent protein phosphatase activities were assessed in cell extracts using a synthetic phosphorylated peptide that is known to serve as a substrate for calcineurin. KEY RESULTS: FK506 was about 100-fold more potent than cyclosporine as an inhibitor of IgE-dependent histamine release from mast cells and basophils. Immunoblotting of solubilized preparations of purified cells demonstrated the presence of calcineurin in mast cells and basophils. In enzyme assays, mast cells expressed approximately 7-fold higher Ca2+-dependent protein phosphatase activity than basophils. Whereas cyclosporine effectively inhibited Ca2+-dependent protein phosphatase activity in cell extracts, FK506 was considerably less effective. CONCLUSIONS AND IMPLICATIONS: FK506 and cyclosporine inhibit the stimulated release of histamine from mast cells and basophils. However, the ability of cyclosporine, but not FK506, to inhibit Ca2+-dependent protein phosphatase activity questions whether FK506 stabilizes mast cells and basophils by interacting with calcineurin.

Basophils↗
PubMed2003

Calcineurin antagonists differentially affect mediator secretion, p38 mitogen-activated protein kinase and extracellular signal-regulated kinases from immunologically activated human basophils.

BACKGROUND: Basophils participate in allergic diseases by invading affected tissues and secreting histamine, leukotriene (LT)C4, IL-4 and IL-13 following FcepsilonRI cross-linking. A reduction of basophil mediator production is therefore of considerable therapeutical interest. Macrolactam derivatives, which inhibit calcineurin activation, may be candidates for antiallergic therapy as they reduce both symptoms of inflammatory skin disease in animal models and mast cell degranulation. OBJECTIVE: To investigate the effects of the calcineurin antagonists ascomycin and cyclosporin A on IgE-dependent mediator release from human basophils. METHODS: Basophils were purified by Ficoll density centrifugation, elutriation and negative selection. Histamine release was measured spectrofluorometrically; LTC4, IL-4 and IL-13 secretions were assayed by enzyme-linked immunosorbent assay (ELISA). Lysed cells were subjected to Western blotting using specific antibodies to phospho-p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)-1 and -2. RESULTS: Ascomycin (0.01 nm to 1 micro m) and cyclosporin A (0.1 nm to 10 micro m) strikingly inhibited (maximally 100%) anti-IgE-induced histamine and cytokine release from basophils, and these actions were unaffected by IL-3 priming. Ascomycin, however, was less potent at blocking LTC4 secretion, whereas cyclosporin A was unable to block production of this mediator. In immunoblotting studies, ascomycin and cyclosporin A reduced IgE-dependent p38 MAPK activation but were less potent at reducing ERK phosphorylation in basophils. CONCLUSION: Calcineurin antagonists like ascomycin and cyclosporin A block IgE-dependent basophil degranulation and cytokine synthesis. Calcineurin may target p38 MAPK activation, but seems to have less activity on ERK phosphorylation. This is paralleled by a reduced or even absent effect of calcineurin antagonists on eicosanoid production.

Basophils↗
PubMed1996

Impairment of the inhibitory effect of sodium on basophil histamine release in patients with systemic sclerosis.

It has been demonstrated that Na+ down-regulates IgE-dependent and IgE-independent histamine release from basophils of normal subjects. The aim of this study was to evaluate whether Na+ exerts its inhibitory effect on basophil histamine release in patients with systemic sclerosis (SSc). Peripheral blood leucocytes were stimulated with anti-IgE, n-formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-3 in the presence of high and low Na+ concentrations, and histamine release was measured by a fluorometric method. The dose-response curves of histamine release induced by the above stimuli were similar in SSc patients (n=15) and in normal subjects (n=39). Na+ removal from the extracellular medium and its isosmotic replacement with choline chloride led to a significant increase of anti-IgE-and fMLP-induced histamine release in normal subjects, but not in SSc patients. In the former population, histamine release induced by an optimal dose of anti-IgE (1/5000) was 26.4+/-3.1% in high Na+ and 59.3+/-3.5% in low Na+ (mean+/-s.e.m., P<0.0001), whereas in the latter population mean histamine release was 20.4+/-5.1% in high Na+ and 15.8+or-2.9% in low Na+ (p NS). A similar trend was observed when basophils were stimulated with fMLP. Na+ exerted a dose-dependent inhibitory effect on anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. IL-3-induced histamine release from basophils of SSc patients was increased in a low-Na+ solution, but to a lesser extent when compared with normal controls. Therefore basophils from normal subjects and SSc patients behave in a different way when stimulated in a low-Na+ medium. The inhibitory effect of Na+ on basophil histamine release is impaired in SSc patients, and this abnormality could contribute to basophil dysfunction.

Aged↗
PubMed2003

In vitro effects of ultraviolet A on histamine release from human basophils.

BACKGROUND: As long-wave ultraviolet (UV) radiation penetrates the dermis, connective tissue cellular components and circulating blood cells can be possible targets for solar UVA. Basophils, involved in the effector phase of the inflammatory response, play a part in skin diseases such as chronic urticaria, psoriasis, atopic dermatitis, fixed drug eruption, allergic contact dermatitis, urticaria pigmentosa, systemic sclerosis and bullous pemphigoid. OBJECTIVE: The evaluation of the in vitro effect of UVA on histamine release from human basophils. METHODS: Basophils from healthy human volunteers were irradiated, respectively, with UVA at doses of 2.5, 5, 7.5, 10, 20 and 50 J/cm2 and then incubated with an anti-IgE serum. A fluorimetric technique was employed to determine histamine release from samples: (i) incubated with 2% HClO4 (complete lysis of basophils); (ii) irradiated with increasing doses of UVA; and (iii) unirradiated (controls). RESULTS: Histamine release was: 100% for HClO4 incubated basophils, 30% for unirradiated and anti-IgE incubated cells (controls) and 27%, 24%, 34%, 41%, 60% and 70% for basophils irradiated with UVA doses, respectively, of 2.5, 5, 7.5, 10, 20 and 50 J/cm2 and incubated with anti-IgE. Histamine releasability from irradiated samples was statistically significant (P < 0.05), in comparison with controls, at UVA doses equal to 5, 10, 20 and 50 J/cm2. CONCLUSIONS: UVA exerts, at least in vitro, a biphasic dose-dependent action on histamine release from human basophils incubated with an anti-IgE serum: at the lowest irradiation doses (< 5 J/cm2) it exerts an inhibitory effect and at the highest doses (> or = 10 J/cm2) histamine release increases significantly.

Basophils↗
PubMed2001

Glucocorticoids induce basophil apoptosis.

BACKGROUND: Induction of apoptosis represents an important mechanism by which glucocorticoids (GCCs) exert their anti-inflammatory properties. The effects of GCCs on apoptosis have been determined in various immune cells and found to vary among different cell types. On the other hand, the effects of GCCs on apoptosis of basophils, active participants in allergic inflammation, have remained obscure. OBJECTIVE: The objective of this study was to investigate the effects of GCCs on basophil apoptosis. METHODS: Basophils were highly purified (purity, >97%) by Percoll density gradient centrifugation followed by negative selection. Cell status was determined by their ability to bind annexin V and exclude propidium iodide. DNA fragmentation was determined by flow cytometry. RESULTS: Dexamethasone (DEX) significantly accelerated the decrease in live cells and increased the number of apoptotic cells in a time-dependent fashion. Light microscopy as well as DNA fragmentation assay confirmed the induction of apoptosis by DEX. A half-maximal effect was observed in a DEX concentration range from 10(-9) to 10(-8) mol/L. Sex steroids did not induce basophil apoptosis at all. DEX also induced basophil apoptosis in the presence of low doses of IL-3. CONCLUSION: GCCs exert potent apoptogenic effects on basophils. GCC-mediated apoptogenic effects on basophils might have implications with respect to the mechanism of action of this class of drugs in allergic disorders.

Apoptosis↗
PubMed2002

Selective expression of nuclear factor of activated T cells 2/c1 in human basophils: evidence for involvement in IgE-mediated IL-4 generation.

BACKGROUND: The nuclear factor of activated T cells (NFAT) family of transcription factors plays a key role in rapidly inducing IL4 gene expression in effector T cells. OBJECTIVE: Because human basophils secrete high levels of IL-4, we have examined whether specific NFAT species are expressed in these cells and whether Fc(epsilon)RI-mediated activation affects their subcellular localization and transcriptional function. METHODS: Intracellular NFAT protein was identified by using 2-color flow cytometry; gene expression was done with RT-PCR. Subcellular localization of NFAT was assessed by means of Western blotting. Electrophoretic mobility shift assays assessed NFAT involvement in IL-4 transcription. RESULTS: Basophils constitutively expressed high levels of NFAT2. In contrast, NFAT1 (NFATp), which is found in most leukocytes, was not seen in basophils. Low-level staining for NFAT4 was detected but was variably expressed among donor cells. Likewise, NFAT2 mRNA was constitutively expressed in basophils, and message for NFAT4 was seen in 3 of 5 preparations, whereas that for NFAT1 was found in only 1 of 5 preparations. NFAT2 protein accumulated in the nuclei of basophils activated for 1 hour with anti-IgE, and this was inhibited with the addition of FK506. A protein-DNA complex was formed with nuclear lysates from basophils and an IL-4 promoter NFAT consensus probe, with greater binding intensities detected in lysates of activated cells. An antibody to NFAT2 reduced the formation of the complex, whereas no effects were seen with antibodies to NFAT1, NFAT4, or unrelated transcription factors. CONCLUSIONS: The selective and specific expression of NFAT2 in basophils is unique among leukocytes. This transcription factor also appears to play a critical role in the Fc(epsilon)RI-mediated production of IL-4 in these cells.

Adult↗
PubMed2003

The release of basogranulin in response to IgE-dependent and IgE-independent stimuli: validity of basogranulin measurement as an indicator of basophil activation.

BACKGROUND: Basogranulin, the novel basophil granule protein recognized by the monoclonal antibody BB1, can be released by stimulation with anti-IgE antibody or calcium ionophore. However, the kinetics and regulation of its secretion are unknown. OBJECTIVE: We quantified basogranulin and histamine release in response to a range of stimuli to assess whether basogranulin secretion is a reliable marker of basophil activation. METHODS: Isolated peripheral blood basophils were stimulated with anti-IgE antibody, calcium ionophore, N -formyl-Met-Leu-Phe, and complement C5a. The released basogranulin and histamine were quantified by dot blotting with BB1 and a fluorometric method, respectively. Basogranulin localization was confirmed by flow cytometry. RESULTS: Both basogranulin and histamine displayed a bell-shaped response curve when basophils were challenged with anti-IgE. Half-maximal release occurred within 30 seconds. Basogranulin levels were maximal by 15 minutes, whereas those for histamine continued increasing to 30 minutes. Wortmannin, a PI3-K inhibitor, suppressed the release of both mediators. Basophils from donors with the "nonreleaser" phenotype secreted neither mediator in response to anti-IgE. Non-IgE-dependent stimuli released both mediators in parallel in a concentration-dependent manner. The correlation between the relative amounts of each mediator released was highly significant (r =.901, P <.0001, n = 87). Flow cytometry revealed that some of the secreted basogranulin adhered to the cell surface. CONCLUSIONS: Basogranulin is secreted along with histamine in response to both FcepsilonR I-related and unrelated stimuli. It is therefore a valid marker of basophil activation and could provide the basis for an immunoassay that distinguishes between basophil and mast cell activation.

Antibodies, Anti-Idiotypic↗
PubMed1990

Interleukin 3 and granulocyte/macrophage-colony-stimulating factor render human basophils responsive to low concentrations of complement component C3a.

Complement component C3a is an anaphylatoxin known to induce plasma exudation and smooth muscle contraction in tissues. The effects on inflammatory effector leukocytes, however, are poorly defined and controversial, being at best weak and occurring at very high C3a concentrations. Here, we examined the effect of C3a upon mediator release from human basophils, with and without pretreatment with interleukin 3 (IL-3), a hematopoietic growth factor recently found to profoundly modify the basophil response to various cell agonists. In the absence of cytokines, C3a, even at a concentration of 1 microM, was ineffective or only weakly stimulatory for basophil mediator release. However, when basophils were pretreated with IL-3 at concentrations of only 0.01-1 unit/ml, they became responsive to C3a, releasing large amounts of histamine and also generating leukotrienes. Surprisingly, almost optimal effects occurred with even very low C3a concentrations (1 nM). Another hematopoietic growth factor, granulocyte/macrophage-colony-stimulating factor (GM-CSF), was also found to render basophils capable of responding to C3a, but the effect was weaker than that of IL-3. C3a-induced histamine release and leukotriene generation occurred rapidly in IL-3-primed cells, being complete after 0.5 and 2 min, respectively. The rapid and strong degranulation response, occurring at very low concentrations of C3a, suggests the presence of a high-affinity C3a receptor on basophils, which might be inducible by cytokines. Our results demonstrate that, depending on the presence of IL-3 or GM-CSF, C3a is a potent basophil activator, and such a phenomenon could be of relevance in various inflammatory processes, especially hypersensitivity reactions.

Basophils↗
PubMed1999

IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils.

IL-18 is a proinflammatory cytokine that plays an important role in natural killer cell activation and T helper 1 (Th1) cell responses. Mast cells and basophils are major inducers and effectors of allergic inflammation. Here we show that basophils and mast cells derived by culture of bone marrow cells with IL-3 for 10 days express IL-18Ralpha chain and that basophils produce large amounts of IL-4 and IL-13 in response to stimulation with IL-3 and IL-18. Injection of IL-12 and IL-18 inhibits IgE production in helminth-infected wild-type mice and abolishes the capacity of their basophils to produce IL-4 and IL-13 in response to stimulation either with IL-3 and IL-18 or with FcepsilonR cross-linkage. By contrast, this combination of cytokines actually increases IgE levels in helminth-infected IFN-gamma(-/-) mice and enhances IL-4 and IL-13 production by their basophils. Furthermore, injection of IL-18 alone enhances basophil production of IL-4 and histamine both in wild-type and IFN-gamma(-/-) mice. Thus, IL-18 has the potential to stimulate basophils but, when given with IL-12, exhibits an antiallergic action in vivo.

Animals↗
PubMed1973

Immunologic rejection of diethylnitrosamine-induced hepatomas in strain 2 guinea pigs: participation of basophilic leukocytes and macrophage aggregates.

The morphologic events associated with the immunologic rejection by strain 2 guinea pigs of ascites variants of two lines of diethylnitrosamine-induced tumors have been studied by light and electron microscopy. Tumor injection sites in the skin of control animals exhibited clusters of viable, actively mitotic tumor cells along with a modest inflammatory infiltrate composed of lymphocytes, macrophages, neutrophils, and rare basophils. In contrast, similar injections of either tumor line in specifically sensitized guinea pigs elicited typical delayed-type skin reactions associated with tumor cell necrosis and a more extensive inflammatory infiltrate including a selective increase in the number of basophilic leukocytes (12%, line 1, or 23%, line 10, of total inflammatory cells). That basophils may have a role in tumor resistance in vivo is suggested by the close anatomic associations observed between basophils and tumor cells, and by the fact that basophils were the only inflammatory cell to demonstrate a relative increase in frequency in the lesions of sensitized as compared with control animals. Moreover, intraperitoneal injection of line 1 tumor in specifically sensitized animals elicited a striking basophilia within 24 h. Unlike macrophages, basophils did not phagocytose tumor cells but did evidence occasional extrusion of granules and frequently exhibited loss of granule staining density, a change that may be related to release of mediator substances. Electron microscope studies of line 1 tumor rejection in the peritoneal cavities of specifically sensitized guinea pigs demonstrated aggregations of "activated" macrophages, lymphocytes, basophils, and damaged or dead tumor cells. These aggregates, held together by complex interdigitations of macrophage villi, closely resembled those occurring in vitro among peritoneal exudate cells whose migration from capillary tubes was inhibited by migration inhibition factor (MIF). Moreover, cells in these aggregates, as well as macrophages inhibited by MIF in vitro, lacked a normal coating of cell surface material.

Animals↗
PubMed1990

Enhancement of human basophil histamine release by interleukin 5.

Substantial evidence indicates a close relationship between eosinophils and basophils. We examined whether interleukin 5 (IL-5), known to be eosinophilopoietic and capable of selectively regulating eosinophil functions, has an affect on basophil functions. IL-5 enhanced basophil histamine release evoked by anti-IgE, formyl-methionyl-leucyl-phenylalanine, or ionophore A23187 at picomolar concentrations. Direct action of IL-5 on human basophils was confirmed using highly purified basophil populations. These observations reveal the novel fact that IL-5 is able to modulate basophil functions as well as eosinophil functions, and suggest that normal human basophils possess functional receptors for IL-5.

Basophils↗