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At least 19 recordsLinked to original sources
PubMed1992

[Characterization of a receptor for interleukin-5 on pulmonary eosinophils with eosinophilic pneumonia].

Interleukin-5 (IL-5) acts on eosinophil differentiation and activation, suggesting the existence of a membrane receptor for IL-5 on eosinophils. Here, we report that 125I-labeled recombinant human IL-5 bound to high affinity receptors on human eosinophils, especially pulmonary eosinophils in eosinophilic pneumonia obtained bronchoalveolar lavage (BAL). No specific binding occurred on neutrophils, nor on the undifferentiated eosinophilic cell line. EoL-3, in the absence of stimulation. The specific binding of IL-5 was induced by incubation at 37 degrees C of human eosinophils and EoL-3 cells with GM-CSF and with the supernatants of BAL cells from patients with eosinophilic pneumonia. These results indicate the existence of a specific binding site for IL-5 on human eosinophils with variable affinity in eosinophil hypodense or normodense subpopulations, as previously reported for other membrane receptors. Furthermore, lung cells (BAL cells) in patients with eosinophilic pneumonia may be involved in the production certain eosinophilopoietic growth cytokines such as IL-3, GM-CSF and IL-5.

Binding Sites↗
PubMed1992

Epstein-Barr virus and interleukin-5 mRNA in acquired immunodeficiency syndrome-related lymphomas with eosinophilia.

Patients infected with the human immunodeficiency virus are at increased risk for developing intermediate-grade and high-grade B-cell lymphomas that in many instances contain Epstein-Barr viral (EBV) DNA. Because interleukin-5 (IL-5), a potent stimulator of eosinophil growth and differentiation, has been detected recently in EBV-infected B-cells, we hypothesized that some acquired immunodeficiency syndrome-related lymphomas with EBV DNA also might contain eosinophilia and IL-5. After reviewing files entered into our archives during the past 3 years, we identified four cases of human immunodeficiency virus-associated, high-grade, B-cell lymphomas that also contained extensive infiltration by eosinophils. Cryopreserved DNA from two of these four cases was available for amplification by the polymerase chain reaction, and both cases yielded an easily identifiable, EBV-specific amplification product. From one of these cases we also were able to extract mRNA and perform messenger amplification phenotyping (MAPPING) for the detection of mRNA coding for IL-5. After reverse transcription of mRNA from this case to cDNA and amplification by the polymerase chain reaction, we identified an amplification product that co-migrated with IL-5-positive controls in an agarose gel. We conclude that some AIDS-related lymphomas are associated with eosinophilia and that the eosinophilia may be related to EBV infection and transcriptional activation of the IL-5 gene.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Interleukin-5 is an autocrine growth factor for Epstein-Barr virus-transformed B lymphocytes.

Because of the recent finding that interleukin-5 (IL-5) is produced by Epstein-Barr virus-transformed B lymphocytes (EBV-B cells), we performed studies to ascertain whether EBV-B cells might use IL-5 by an autocrine mechanism. EBV-B cells known to be IL-5 producers were capable of responding to addition of exogenous IL-5 by dose-related augmented proliferation. The addition of a neutralizing anti-IL-5 antibody reduced these effects and also dose-dependently inhibited proliferation and reduced viability of unsupplemented EBV-B cells, having a maximum effect at about 120 hours. In contrast, no stimulatory effect of IL-5 was noted on Burkitt's lymphoma cell lines, nor were these lines growth-inhibited by anti-IL-5 antibody. With biotinylated IL-5, (b-IL-5) second labeling with streptavidin-FITC, and flow cytometric analysis, binding of IL-5 to EBV-B cells cultured in fresh medium was demonstrated and could be competed for by excess unlabeled IL-5, suggesting the presence of IL-5-specific binding sites. Binding of IL-5 was reduced on cells cultured for longer periods before study but could be restored by extensively washing cells before labeling them with b-IL-5, suggesting that surface binding sites had become occupied by endogenously produced IL-5. These findings support a role for IL-5 in autocrine support of EBV-B cell growth.

Antibodies↗
PubMed1992

Interleukin-5 selectively enhances the chemotactic response of eosinophils obtained from normal but not eosinophilic subjects.

We have attempted to determine whether interleukin-5 (IL-5), a cytokine that selectively affects eosinophil (as opposed to neutrophil) differentiation and activation, also modulates eosinophil migrational responses. Using a modified Boyden chemotaxis assay, IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) gave a weak locomotory response for eosinophils from normal nonatopic subjects (optimal at 10(-11), 10(-8), and 10(-9) mol/L, respectively), but not for eosinophils from subjects with an eosinophilia associated with asthma and/or allergic rhinitis. In contrast, IL-5 and IL-3 had no effect on neutrophils, while GM-CSF was chemotactic for neutrophils over a limited concentration range, optimal at 10(-8) mol/L. When eosinophils from normal subjects were incubated with IL-5 (10(-9) mol/L), the locomotory response to platelet-activating factor (PAF; 10(-8) mol/L, P less than .05), leukotriene B4 (LTB4; 10(-6) mol/L, P less than .01), and N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10(-8) mol/L, P less than .01) was significantly enhanced. The percentage enhancement of eosinophil locomotion by IL-5 was greater for eosinophils from normal as compared with subjects with an eosinophilia associated with asthma (P less than .05 for PAF and LTB4; P less than .01 for FMLP). Preincubation of eosinophils from normal subjects with IL-5 (10(-9) mol/L) attenuated the subsequent locomotory response to IL-5 (10(-12) and 10(-11) mol/L, P less than .05). Therefore, the observed refractoriness of eosinophils from eosinophilic subjects to both directional migratory and priming effects of IL-5 in vitro, may reflect a deactivation process resulting from prior exposure in vivo. The selective priming of eosinophil but not neutrophil locomotion by IL-5 suggests that this cytokine may play a significant role in the preferential accumulation of eosinophils at sites of allergic inflammation.

Asthma↗
PubMed1992

Murine mucosal T cells have VIP receptors functionally distinct from those on intestinal epithelial cells.

Reports suggest that vasoactive intestinal peptide (VIP) binds to lymphocytes and modulates immune responses. The intestines are richly innervated with VIP-producing nerves. Thus, VIP from nerves or other sources may participate in mucosal immunoregulation. To explore this hypothesis further, murine intestinal mucosal inflammatory cells were scrutinized for functional VIP receptors. An [125I]VIP competitive binding assay characterized VIP receptors. Unfractionated lamina propria inflammatory cells bound [125I]VIP specifically. This binding was abrogated by T cell depletion. The VIP receptor on lamina propria T cells was of a single class with a Kd of 9.08 x 10(-9) M. It bound PHI and other peptide analogs poorly. The intestinal epithelial cell had a high-affinity VIP receptor (Kd 4.17 x 10(-10) M) that bound one VIP analog with moderate affinity. Both VIP and ConA stimulated mucosal inflammatory cells to release interleukin-5 (IL-5). Mucosal inflammatory cells depleted of T cells did not release IL-5 in response to VIP or ConA. It is concluded that: (1) some murine mucosal T lymphocytes have VIP receptors that may be distinct from those displayed on mucosal epithelial cells; (2) VIP affects mucosal T lymphocyte function.

Animals↗
PubMed1992

Adult T cell leukemia associated with eosinophilia: analysis of eosinophil-stimulating factors produced by leukemic cells.

The mechanism of eosinophilia in a patient with adult T cell leukemia (ATL) was investigated. A 61-year-old woman with ATL presented marked eosinophilia. No parasite infections or allergic diseases were found in this patient. The number of eosinophils fluctuated in parallel with that of ATL cells during her clinical course. The patient's serum and the culture supernatant of ATL cells showed eosinophil colony-stimulating activity. Northern blot analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5), which are known eosinophil CSFs, showed that only GM-CSF but not IL-3 or IL-5 was expressed in freshly separated and cultured ATL cells. Since neutrophil and monocyte numbers did not increase, it is suggested that GM-CSF and unknown cytokines other than IL-3 and IL-5 produced by ATL cells synergistically stimulated eosinophil precursors in the present case.

Blotting, Northern↗
PubMed1992

The identification of an eosinophil differentiation factor in culture supernatant of mononuclear cells from asthmatics.

Although peripheral eosinophilia is a common feature of bronchial asthma, the precise mechanism of its production is still unknown. It has recently been reported that murine interleukin-5 (IL-5) can cross-react with human cells and selectively stimulates the proliferation and differentiation of eosinophils. This study identified the IL-5-like activity in culture supernatants of peripheral blood mononuclear cells (MNCs) from asthmatic patients. Murine recombinant IL-5 (rIL-5) was used as a positive control; the number of eosinophils was determined by both Wright's stain and eosinophil peroxidase measurement. Time course and dose response studies showed that rIL-5 at 40 U/ml induced a maximal eosinophil differentiation after a three week incubation with cord blood MNCs. Unstimulated MNC supernatants obtained from asthmatics possessed a higher eosinophil differentiation activity (OD490, 0.09 +/- 0.02, n = 23) than those obtained from the normals (0.03 +/- 0.01) (P < 0.02). This activity in unstimulated MNC supernatant can be neutralized by anti-IL-5 antibodies. Neither Bermuda grass- nor phytohemagglutinin-stimulated MNC supernatant showed a statistical significance between these two groups. The IL-5-like activity was associated with a protein of MW around 30kD as determined by Superose-12 PG gel filtration. In conclusion, MNC culture supernatants derived from asthmatics contained an eosinophil differentiation activity, which might be important for regulation of eosinophil generation and thus contribute to the asthma-related eosinophilia.

Asthma↗
PubMed1992

Regeneration of autotransplanted splenic tissue at different implantation sites.

Inbred animals (Lewis rats) were used to investigate the regeneration of autologously implanted splenic tissue at intra-omental and subcutaneous sites. Quantitative immunohistology with monoclonal antibodies against lymphocytes and macrophages was performed to analyse the cell density of red pulp (RP), periarteriolar lymphoid sheath (PALS), marginal zone (MZ) and follicle, 7-180 days after transplantation. Antigenic, allogeneic and mitogenic stimulation and Northern blotting were also performed. Transplant groups differed from spleen only in the reduced size of PALS; however, quantitative analysis demonstrated subtle differences between spleen and transplants. The cell density of B-cells and ED-1+ macrophages was reduced in the RP, Tsupp/cyt-cells were decreased and B-cells increased in PALS, and B-cells and Thelper-cells reduced in the MZ. No differences could be detected between the transplant groups. Flow-cytometric analysis of cell suspensions from spleen and transplants revealed a reduction of T-cells (OX-19+), MHC-I and transferrin-receptor-bearing cells in both transplant groups, and a decrease in the number of Thelper-cells and ED-3+ macrophages in subcutaneous transplants. Both transplant groups were defective regarding the allogeneic and pokeweed mitogen response. Aberration of the lipopolysaccharide response was restricted to subcutaneous transplants, which additionally showed abnormal expression of interferon-gamma, interleukin-5 and interleukin-6 mRNA. Thus, subtle alterations of the newly developed microenvironment and/or lymphocyte-homing may influence the regeneration of splenic tissue; the implantation site may represent an important parameter in functional reorganisation.

Animals↗
PubMed1992

Dual function of eosinophils in pathogenesis and protective immunity against parasites.

The functional duality of eosinophils, involved in a protective response or in pathogenesis is illustrated in various parasitic infections. In schistosomiasis, eosinophils have been shown to mediate schistosomula killing, in the presence of antibodies. The association of eosinophil-dependent cytotoxic antibody isotypes with resistance of reinfection (IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, suggested a participation of eosinophils in antibody-dependent protective response. However eosinophils could participate to granuloma formation and consequently to the pathological reactions during schistosomiasis. Activation of eosinophils by antibodies, leading to release of granule proteins have been studied in patients with filariasis. Eosinophil peroxidase, EPO was released after IgE-dependent activation whereas Eosinophil Cationic Protein, ECP, was released after IgG- and IgA-dependent activation of eosinophils, results suggesting a process of differential release of mediators. Interactions between eosinophils and interleukins, and specially IL-5 are discussed. Whereas a receptor for IL-5 has been characterized on human eosinophils, recent studies have shown that eosinophils expressed the messenger RNA encoding IL-5. These results associated to data showing the synthesis of other cytokines indicate that eosinophils are not only the source of cytotoxic mediators involved in the effector phase of immunity but also of growth and regulatory factors, participating to immunoregulation.

Animals↗
PubMed1992

Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects.

The cytokine secretion profiles of T cell lines (TCL) specific for purified protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great majority of PPD-specific TCC derived from nonatopic individuals did not produce IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic individuals are able to produce IL-4 and IL-5 in response to bacterial antigens, such as PPD and SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.

Adult↗
PubMed1992

Effects of IL-4, IL-5, and IL-6 on growth and immunoglobulin production of Epstein-Barr virus-infected human B cells.

In the present study we investigated whether interleukin-4 (IL-4), IL-5, and IL-6 could enhance the efficiency of Epstein-Barr virus (EBV) transformation for the generation of specific human monoclonal antibody (HuMAb)-producing B-cell lines directed against erythrocyte Rhesus(D) antigen. In newly EBV-infected B cells, IL-4 and IL-6 caused a comparable enhancement of proliferation and of total IgG and IgA production. IL-6 showed a much stronger effect than IL-4 on IgM production, whereas IL-4 was unique in inducing IgE production. No stimulatory effects of IL-5 on either growth or Ig production were observed. Although addition of IL-6 resulted during the early phase after EBV infection in high numbers of Ag-specific antibody-producing wells, this did not result in an increased number of stable HuMAb-secreting cell lines. When the effects of cytokines were tested on established polyclonal EBV B cells, in a high cell density culture system, only IL-6 was able to enhance Ig secretion, while no effect could be demonstrated on proliferation. These studies substantiate that IL-6 is an important regulator of proliferation and Ig production, and that it acts at distinct stages after EBV infection, but does not increase the final overall recovery of Ag-specific EBV B-cell lines.

Antibody Formation↗
PubMed1992

Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season.

The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.

Adolescent↗
PubMed1992

Ligand-induced phosphorylation of the murine interleukin 3 receptor signals its cleavage.

The murine interleukin 3 receptor (mIL-3R) is a heterodimer consisting of a 70-kDa alpha subunit and one of two alternative 120-kDa beta subunits termed beta IL-3 and beta c. beta IL-3 (originally called Aic2A) is capable of binding mIL-3 by itself, whereas beta c (Aic2B) does not bind any ligand on its own but increases the affinity of mIL-3, murine granulocyte/macrophage-colony-stimulating factor, and mIL-5 for their respective alpha subunits. Interestingly, although the mIL-3R does not possess tyrosine kinase activity, its beta IL-3 subunit does become tyrosine phosphorylated upon binding mIL-3. To further investigate the properties of this subunit, we have purified it from the cell line B6SUtA1, which expresses a high level of mIL-3R. Intriguingly, studies comparing the stability of the 140-kDa, tyrosine-phosphorylated form of this subunit with its 120-kDa, non-tyrosine-phosphorylated form reveal that the former is far less stable and is rapidly degraded to a 70-kDa fragment. Mixing experiments demonstrate that the differential stability of the two forms is due to an intrinsic difference in protease susceptibility. Phosphatase studies indicate that the higher protease susceptibility of the tyrosine-phosphorylated beta IL-3 is due to the presence of both phosphotyrosine and phosphoserine residues. Western analyses using an anti-N-terminal mIL-3R beta IL-3 chain antibody reveal that this proteolytic cleavage also occurs rapidly in intact cells following stimulation with mIL-3 and occurs at the cell surface, since it takes place within minutes at 37 degrees C, is observed with purified plasma membranes, and is not inhibited by chloroquine. This degradative step may play an important role in the mechanism of action of mIL-3.

Alkaloids↗
PubMed1992

Activation of B lymphocytes by NK cells.

The ability of NK cells to induce differentiation of B lymphocytes to IgM secretion in vitro has been investigated. Homogeneous preparations of NK cells obtained from IL-2 propagated splenocytes from SCID mice were found to have the ability to induce resting B lymphocytes to proliferate and secrete significant amounts of IgM. The induction is greatly enhanced by the presence of both IL-2 and IL-5 and does not require T lymphocytes or adherent cells in the responding population. Cell contact between the two populations is not necessary suggesting that the effect is mediated by soluble factor(s) which can be produced even by irradiated NK cells. Because the activity cannot be replaced by either r-tau-IFN or tumor necrosis factor-alpha or inhibited by antibodies to these lymphokines, a novel NK cell-derived factor(s) may be involved. The implications of this interaction between NK cells and B lymphocytes are discussed.

Animals↗
PubMed1992

Cytokine receptors: structure and signal transduction.

In the past 2-3 years, a number of cytokine receptors have been partly characterized and the cDNAs for the ligand binding chains cloned. This has revealed that cytokine receptors are complex. Many are known to be multichain receptors (e.g. IL-2) and since their mechanism of signal transduction is not obvious, it is likely that other proteins yet to be defined take part in the signalling process. The cloning of the receptor ligand binding chain has revealed that (unlike cytokines), there are major families of receptors. Some are members of the Ig supergene family (e.g. IL-1 receptor), others are members of the nerve growth factor receptor family (e.g. TNF), but the majority are members of the haematopoietic growth factor family (e.g. IL-3, GM-CSF). Yet other cytokine receptors do not belong to a family, e.g. IFN-gamma.

Amino Acid Sequence↗