PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Receptors, Interleukin-5”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

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

Chromosomal localization and organization of the murine genes encoding the beta subunits (AIC2A and AIC2B) of the interleukin 3, granulocyte/macrophage colony-stimulating factor, and interleukin 5 receptors.

Chromosomal genes for two mouse homologous beta subunits (AIC2A and AIC2B) of the interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin-5 receptors were characterized. Both AIC2A and AIC2B genes were present on a 250-kilobase MluI restriction fragment and were mapped on murine chromosome 15 (these loci were provisionally designated as Il3rb-1 (AIC2A) and Il3rb-2 (AIC2B)), closely linked to the c-sis locus. Both genes consist of 14 exons and span about 28 kb each. The major transcription initiation sites of both genes were mapped at 194 bp from the initiation codon. These genes are 95% identical up to 700 bp from the transcription initiation sites. Potential recognition sequences for hemopoietic transcription factors including GATA-1 and PU.1 in addition to a TATA-like sequence are present in the 5'-flanking region. A stretch of 20 bp including the initiation site is homologous to the corresponding region of the erythropoietin receptor and the interleukin-7 receptor genes and to the initiator sequence of the adeno-associated virus P5 promoter, suggesting a possible role in transcription initiation. Comparison of the exon/intron boundaries of AIC2A and AIC2B genes with those of other members of the cytokine receptor superfamily reveals a conserved evolutionary structure. Isolation of various forms of AIC2 cDNAs reveals differential splicing of the transcripts.

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↗
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

Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation.

The high-affinity receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3) and interleukin 5 (IL-5) are composed of two distinct subunits, alpha and beta c. The alpha subunits are specific for each cytokine, whereas the beta subunit (beta c) is shared by the three receptors and is an essential component of signal transduction. We have made a series of mutant beta c cDNAs that delete various regions of the cytoplasmic domain and examined the function of these mutants by coexpressing them with the alpha subunit of the human GM-CSF receptor (hGMR) in an IL-3-dependent mouse pro-B cell line BaF3. Two domains in the membrane-proximal portion of beta c were found to be important for transducing the hGM-CSF-mediated growth signals: one domain between Arg456 and Phe487 appears to be essential for proliferation, and the second domain between Val518 and Asp544 enhances the response to GM-CSF, but is not absolutely required for proliferation. The region between Val518 and Leu626 was responsible for major tyrosine phosphorylation of 95 and 60 kDa proteins. Thus, beta c-mediated major tyrosine phosphorylation of these proteins was apparently separated from proliferation. However, the beta 517 mutant lacking residues downstream of Val518 transmitted a herbimycin-sensitive proliferation signal, suggesting that beta 517 still activates a tyrosine kinase(s). We also evaluated the role of the cytoplasmic domain of the GMR alpha subunit and the results suggest that it is involved in the hGM-CSF-mediated signal transduction, but is not essential.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
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

Role of the interleukin 5 receptor system in hematopoiesis: molecular basis for overlapping function of cytokines.

Interleukin 5 (IL-5) is a kind of peptide hormone released from T lymphocytes of mammals infected with microorganisms or parasites. It is an acidic glycoprotein with a molecular mass of 40 to 50 kDa that consists of a homodimer of polypeptides. It controls hematopoiesis so that it increases natural immunity. In the mouse, IL-5 acts on committed B cells to induce differentiation into Ig-producing cells and on common progenitors for CD5+ pre-B cells and CD5+ macrophages to support their survival. The antibodies secreted by CD5+ B cells seem to be responsible for the primary protection against the infection with microorganisms or parasites. It also supports the growth and/or differentiation of eosinophil precursor and mature eosinophils, which can be effective for the removal of parasites in combination with the antibodies against them. Murine IL-5 receptor (IL-5R) consists of two different polypeptide chains; alpha chain and beta chain. The IL-5R alpha chain is 60 kDa protein that binds IL-5 with low affinity. The IL-5R beta chain is a 130 kDa protein which does not bind IL-5 by itself but is necessary to form the high affinity IL-5R. The beta chain was identified by using one of the anti-IL-5R mAb and anti-IL-3R mAb as the IL-3R homologue. This beta chain is also used as the beta chain of GM-CSF receptor. This fact suggests that there is a common signaling mechanism among these cytokines and efficient cooperation among them. At the same time, these findings may explain the overlapping role of these cytokines in the development of granulocytes.

Animals↗
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

IL-2 and a contact-mediated signal provided by TCR alpha beta + or TCR gamma delta + CD4+ T cells induce polyclonal Ig production by committed human B cells. Enhancement by IL-5, specific inhibition of IgA synthesis by IL-4.

To study the role of T cells in T-B cell interactions resulting in isotype production, autologous purified human splenic B and T cells were cocultured in the presence of IL-2 and Con A. Under these conditions high amounts of IgM, IgG, and IgA were secreted. B cell help was provided by autologous CD4+ T cells whereas autologous CD8+ T cells were ineffective. Moreover, CD8+ T cells suppressed Ig production when added to B cells cocultured with CD4+ T cells. Autologous CD4+ T cells could be replaced by allogeneic activated TCR gamma delta,CD4+ or TCR alpha beta,CD4+ T cell clones with nonrelevant specificities, indicating that the TCR is not involved in these T-B cell interactions. In contrast, resting CD4+ T cell clones, activated CD8+, or TCR gamma delta,CD4-,CD8- T cell clones failed to induce IL-2-dependent Ig synthesis. CD4+ T-B cell interaction required cell-cell contact. Separation of the CD4+ T and B cells by semiporous membranes or replacement of the CD4+ T cells by their culture supernatants did not result in Ig synthesis. However, intact activated TCR alpha beta or TCR gamma delta,CD4+ T cell clones could be replaced by plasma membrane preparations of these cells. Ig synthesis was blocked by mAb against class II MHC and CD4. These data indicate that in addition to CD4 and class II MHC Ag a membrane-associated determinant expressed on both TCR alpha beta or TCR gamma delta,CD4+ T cells after activation is required for productive T-B cell interactions resulting in Ig synthesis. Ig production was also blocked by mAb against IL-2 and the IL-2R molecules Tac and p75 but not by anti-IL-4 or anti-IL-5 mAb. The CD4+ T cell clones and IL-2 stimulated surface IgM-IgG+ and IgM-IgA+, but not IgM+IgG- or IgM+IgA- B cells to secrete IgG and IgA, respectively, indicating that they induced a selective expansion of IgG- and IgA-committed B cells rather than isotype switching in Ig noncommitted B cells. Induction of Ig production by CD4+ T cell clones and IL-2 was modulated by other cytokines. IL-5 and transforming growth factor-beta enhanced, or blocked, respectively, the production of all isotypes in a dose-dependent fashion. Interestingly, IL-4 specifically blocked IgA production in this culture system, indicating that IL-4 inhibits only antibody production by IgA-committed B cells.

Antibody Formation↗
PubMed1992

Schistosoma mansoni eggs induce antigen-responsive CD44-hi T helper 2 cells and IL-4-secreting CD44-lo cells. Potential for T helper 2 subset differentiation is evident at the precursor level.

Schistosoma mansoni eggs are potent inducers of biased Th2-like immune responses. Using a model system where mice are immunized with isolated schistosome eggs, we demonstrate that CD44 expression, up-regulation of which has been linked to Th cell development, is increased on Th2 cells. We also investigate the functional properties of CD44-lo Th cells recovered from the overtly Th2 environment constituted by lymph nodes draining sites of egg deposition. Production of high levels of IL-4, IL-5, and IL-10 by Th cells responding to egg Ag is shown to be the property of a subpopulation expressing CD44-hi. This population of Th cells cosegregates with a blasting subpopulation expressing more IL-4R (but similar amounts of IL-2R) than Th cells from normal mice. These results indicate that mature Th2 cells responding to schistosome eggs are CD44-hi and suggest that they use IL-4 as a growth factor. In contrast, CD44-lo cells sorted from lymph node populations responding to eggs are able to produce small amounts of IL-4 and IL-2, but no IL-5 or IL-10. This is surprising, because low expression of CD44 is considered a characteristic of Th cell naivite and concomitant ability to produce only IL-2. Thus, in lymph nodes responding to schistosome eggs, potential for Th2 subset differentiation is evident within the CD44-lo precursor Th subpopulation.

Animals↗
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

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

Interleukin-1 induces protein tyrosine phosphorylation in T cells.

Interleukin (IL)-1 alpha activates multiple signal transmission pathways in the T helper type 2 cell line, D10A, and these pathways are linked to two separate IL-1 receptors (IL-1R). In the present report we show that IL-1 induces the activation of tyrosine kinase in these cells, leading to tyrosine phosphorylation of a subset of proteins of 38, 75, 97 and 115 kDa. This type of phosphorylation is prevented by a monoclonal antibody directed against the 80-kDa IL-1R and by tyrphostins which are specific inhibitors of tyrosine kinases. In addition, this inhibitor blocks IL-1-and IL-2-induced proliferation in D10A cells as well as the c-myc and c-myb proto-oncogene mRNA expression in response to IL-1. Interestingly, the inhibitor of cAMP-dependent kinase, H-8, only blocks IL-1-induced c-myb, but not c-myc mRNA expression. Altogether, our results demonstrate that the activation of a tyrosine kinase(s) is an early and major event that happens after IL-1/IL-1R interaction, leading to an increase in intracellular cAMP which results in c-myb and IL-5 mRNA expression. Independent of cAMP, by tyrosine phosphorylation of specific substrates IL-1 also induces c-myc and IL-6 mRNA expression and cellular proliferation.

Animals↗
PubMed1992

The requirements for growth of in vivo activated autoimmune B cells are similar to those of in vitro generated lipopolysaccharide B cell blasts and dissimilar to anti-IgM plus IL-4 induced B lymphoblasts.

The requirements for growth of in vivo activated B cells (natural blasts) from autoimmune NZB/W mice and of B cells from the same animals activated in vitro with either LPS or anti-IgM plus IL4 (mimicking 'in vitro' antigen induced TH cell-B cell interaction) were studied comparatively. The proliferation of natural and LPS blasts was inhibited by anti-IgM antibodies and augmented by recombinant IL-5. In contrast, anti-IgM stimulated the growth of anti-IgM plus IL-4 primed B cells but was without effect on the proliferative responses in the presence of IL-5. The growth inhibition induced by anti-IgM signalling on natural and LPS blasts seemed to be due to cross-linking of sIg rather than to binding of anti-IgM antibodies to the Fc receptors since a similar effect was observed with the F(ab)'2 fragment of this molecule. Maximum proliferation was obtained by a combination of IL-4 and IL-5 in natural and LPS blasts, whereas peak responses in anti-IgM plus IL-4 blasts were achieved by a combination of anti-IgM and IL-4. Lymphoblasts recovered after preculturing natural blasts in medium alone (more differentiated in vivo activated B cells) displayed high spontaneous proliferation which was strongly inhibited by anti-IgM. This inhibition was reversed partially by IL-4 and totally by IL-5. To define better the role of BLy+ cells in the spleen of NZB/W mice, purified Ly1+ and Ly1- cells, obtained by separation using magnetic beads, were analysed. The growth of both cell subpopulations was inhibited by anti-IgM and enhanced by IL-5. Cytotoxic elimination of Ly1+ cells from the primed B blast populations did not modify the proliferative pattern of these cells. Our results show that the growth requirements of in vivo activated autoimmune B cells resemble those of LPS blasts and differ from those following stimulation with anti-IgM plus IL-4, suggesting that B cells in systemic autoimmune diseases may have been activated by polyclonal stimulation. Nevertheless, other mechanisms for autoimmune B cell activation cannot be ruled out by the present experimental approach.

Animals↗