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Biomedical subjects

A Billiau

Publications and source records attributed to A Billiau.

At least 127 records · Page 7Linked to original sources
PubMed1989

Identification by sequence analysis of chemotactic factors for monocytes produced by normal and transformed cells stimulated with virus, double-stranded RNA or cytokine.

A monocyte chemotactic activity was found to be released by various types of cultured human cells after appropriate stimulation: normal diploid fibroblasts, peripheral blood mononuclear cells or monocytes isolated therefrom, and a number of tumor cell lines, including osteosarcoma (MG-63) and hepatoma (Malavu) but not melanoma (Bowes) cells. Cultures of diploid human fibroblasts and these tumor cells stimulated with interleukin (IL) 1 or double-stranded RNA [poly(rI).poly(rC)], or infected with viruses (measles or rubella viruses) were found to produce chemotactic activity for both monocytes and granulocytes. Media collected from fibroblasts treated with E. coli or IL 6 did not contain such activity. Granulocyte and monocyte chemotactic activities were serologically distinct, and could be separated by successive chromatographical procedures. While the granulocyte chemotactic activity of both fibroblasts and MG-63 cells had previously been identified as granulocyte chemotactic protein/IL 8, the monocyte chemotactic activity from MG-63 cells was identified by amino acid sequence analysis as a different protein recently described to be released by human glioma and myelomonocytic cell lines. In view of the similarity in their chromatographical behavior, monocyte chemotactic activities from fibroblasts, MG-63 cells and fresh monocytes can probably be assigned to identical molecules. Cultures of unfractionated peripheral blood cells, however, were found to release an additional monocyte chemotactic protein, identifiable by amino acid sequence analysis as platelet factor 4.

Amino Acid Sequence↗
PubMed1989

Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor.

Experimental cerebral malaria (ECM), a lethal hyperacute neurological syndrome associated with high blood levels of tumor necrosis factor, develops in genetically susceptible (CBA/Ca) mice 7 days after infection with Plasmodium berghei ANKA strain. Injections of neutralizing monoclonal antibody against recombinant murine interferon gamma, not later than 4 days after infection, markedly reduced the incidence of ECM and the elevation in serum levels of tumor necrosis factor. This treatment prevented the cerebral lesions (plugging of brain vessels by monocytes, lymphocytes, and parasitized erythrocytes). In contrast, the extent of macrophage infiltration in lymphoid organs (which is a characteristic feature of mice developing ECM), as well as the course of infection, remained unaffected by the antibody treatment. Protected mice died at a later time of severe anemia and overwhelming parasitemia, the usual outcome of P. berghei infection in mice that are not susceptible to ECM. The present data indicate that interferon gamma constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon gamma released by activated CD4+ T cells acts by augmenting both production and action of tumor necrosis factor.

Animals↗
PubMed1989

Recombinant interferon-gamma induces HLA-DR expression on human corneal epithelial and endothelial cells in vitro: a preliminary report.

The effect of interferon-gamma on the expression in situ of major histocompatibility complex (MHC) products in human corneas was studied in vitro. Incubation for four days with 5 or 50 mg/l of Escherichia coli-derived recombinant human interferon-gamma resulted in the appearance de novo of MHC class II or HLA-DR antigens on variable numbers of corneal epithelial cells as well as on corneal endothelium, whereas it had no effect on the expression of MHC class I or HLA-ABC antigens. These results may help to explain the mechanism underlying the expression of HLA-DR antigens on corneal and limbal epithelium in various inflammatory eye diseases.

Cells, Cultured↗
PubMed1989

Production of interleukin-6 by folliculo-stellate cells of the anterior pituitary gland in a histiotypic cell aggregate culture system.

Reaggregate cell cultures of mouse or rat anterior pituitary were found to produce interleukin-6 (IL-6), a cytokine known for its multiple actions in the immune system. Studies on aggregates prepared from differentially enriched pituitary cell populations revealed the presence of folliculo-stellate (FS) cells to be essential for IL-6 production. Aggregates that contained only hormone-secreting, but no FS cells, failed to produce IL-6. Furthermore, the yield of IL-6 increased with increasing proportions of FS cells present in the aggregates. It is suggested that IL-6 participates in the local regulation of the secretory function of the hypophysis and may constitute a link between events in the immune system and those in the endocrine system.

Animals↗
PubMed1989

The potential role of interferons and interferon antagonists in inflammatory disease.

Studies indicate that, among a number of other cytokines, interferons (IFN alpha, beta and gamma) are important elements regulating acute as well as chronic inflammatory responses. The role of interferons has been investigated in various experimental models of inflammation, by administration both of interferons and of antibodies that block the biological activity of interferons formed endogenously. The conclusions reached from these experiments clearly indicate that interferons can boost as well as inhibit inflammation. The effects depend on the type of inflammation studied, the time of interferon administration or emergence in the tissue, the type of interferon (alpha/beta or gamma), the dosage, and the presence of other inflammation-controlling cytokines. The effect of blockage of IFN gamma by the systemic administration of neutralising antibodies is particularly clear. Such blockage has been found to profoundly modify local lipopolysaccharide (LPS)-induced inflammation, brain inflammation due to autoimmunity or infection, and shock reactions caused by systemic administration of LPS. Further research on the particular place occupied by interferons in the inflammation-controlling cytokine network holds great promise, not only for better understanding but also for improved therapy of acute and chronic inflammatory disease.

Animals↗
PubMed1989

Interferon-gamma is cytotoxic for normal mouse fibroblasts: enhancement by tumor necrosis factor and interleukin 1.

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are cytotoxic for certain tumor cells but have a proliferative effect on normal cells. Here we show that interferon-gamma (IFN-gamma) can be cytotoxic for normal cells, in particular mouse embryonic fibroblasts. The cytotoxicity effect is observed with immuno-purified recombinant mouse IFN-gamma (MuIFN-gamma) at concentrations of 1,000 I.U./ml and can be neutralized by anti-MuIFN-gamma monoclonal antibodies. The effect appears 48 h after initial contact with IFN-gamma and is not influenced by infection of the target cells with mengovirus. Although TNF and IL-1 are not toxic for mouse fibroblasts, they can strongly enhance the IFN-gamma-induced cytotoxicity. Interferon-alpha (IFN-alpha), interferon-beta (IFN-beta) and interleukin-6 (IL-6) neither are cytotoxic themselves nor have any influence on the IFN-gamma-induced cytotoxicity. The cytotoxicity of IFN-gamma, in contrast to that of TNF is inhibited by actinomycin or cycloheximide. These data suggest that the cytotoxic effect of IFN-gamma requires active cooperation of target cells and that the mechanism of action is different from that of the TNF-induced cytotoxicity.

Animals↗
PubMed1989

The role of cytokines in various animal models of inflammation.

Studies are reviewed in which the role of IFN-gamma in different models of inflammation in mice is examined: LPS-induced generalized Shwartzman reaction, experimental allergic encephalomyelitis (EAE) and experimental cerebral malaria (ECM). The particular role of the cytokine was studied by systemic administration and by blocking the endogenously produced cytokine by the use of neutralizing antibodies. IFN-gamma was found, depending on the model and circumstances, to exert an anti- or a pro-inflammatory effect. In the generalized Shwartzman reaction and ECM this cytokine has a disease promoting role. In EAE, on the contrary, endogenous as well as exogenous IFN-gamma exert a down-regulating effect.

Animals↗
PubMed1988

Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal.

T cell proliferation induced by the lectin PHA requires the presence of monocytes. Here, we report that IL-6 represents part of the monocyte-derived helper activity for human T cell stimulation with PHA. Resting T cells isolated from peripheral blood or tonsils and completely depleted of accessory cells (monocytes and NK cells) did not proliferate in response to PHA alone. Addition of a cell-free monocyte culture supernatant (not containing IL-2) to the PHA-stimulated cultures resulted in T cell proliferation. We identified IL-6 as an essential helper factor in these monocyte supernatants, because antisera to IL-6 (but not anti-IL-1-beta) completely neutralized the helper effect of the monocyte supernatant. Moreover, addition of purified human IL-6 (but not IL-1-beta) to T cell cultures resulted in proliferation of PHA-stimulated T cells. Although IL-1 could not restore the PHA-induced proliferative response of isolated T cells by itself, it strongly enhanced the helper effect of IL-6. In contrast to intact monocytes, IL-6 did not induce detectable IL-2 production in cultures of PHA-stimulated T cells. Furthermore, an anti-IL-2R mAb (anti-Tac) did not block the proliferative response induced by PHA and IL-6, suggesting that an IL-2-independent pathway of T cell proliferation was involved. In conclusion our results show that human IL-6, previously identified as a B cell hybridoma growth and a B cell differentiation factor, represents part of the monocyte helper function for PHA-induced human T cell activation and proliferation.

Adult↗
PubMed1988

Heterogeneity of human tissue-type plasminogen activator.

Tissue-type plasminogen activator (t-PA) from human melanoma cells (Bowes) was purified by immunosorbent chromatography on affinospecific polyclonal antibodies and gel filtration in the presence of KSCN. The immunosorbent eluate contained three major components of greater than 200, 85 and 65 kDa, respectively. The 65 kDa t-PA component could be separated by gel filtration on Ultrogel AcA44 in the presence of KSCN to a pure preparation yielding a unique N-terminal amino acid sequence. Immunoblot analysis, using affinospecific antibodies against t-PA, was a specific and sensitive method to identify different types of t-PA (I-IV), as well as t-PA-inhibitor complexes and degradation products in unstimulated melanoma cell culture fluids. Furthermore, the t-PA preparations, produced by phorbol ester-treated melanoma cells, were free of type IV and thus differed physiochemically from the constitutively produced t-PA preparations. The composition of t-PA from mammalian cell cultures is thus more complex than hitherto described.

Animals↗
PubMed1988

Cooperation between an anti-T cell (anti-CD28) monoclonal antibody and monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2.

CD28 is an Ag of 44-kDa Mr that is expressed on the membrane of the majority of human T cells and that is recognized by mAb 9.3. The functional effects of mAb 9.3 on peripheral blood T cells were studied. mAb 9.3 was not mitogenic, unless it was combined with PMA. When CD28 was cross-linked after binding of mAb 9.3 to the T cell by immobilized or soluble anti-mouse IgG, T cells proliferated in response to rIL-2, provided that monocytes were also present. The additional signal required for IL-2 responsiveness after cross-linking of CD28 could also be delivered in cultures of purified T cells by a cellfree monocyte culture supernatant. Expression of IL-2R on about 10% of the T cells was demonstrated by staining with an anti-IL-2R mAb, and was found to be largely restricted to CD4+ cells. The active compound responsible for the helper signal in the monocyte culture supernatant was identified as IL-6 because purified IL-6 (but not IL-1 beta) had similar activity and because an antiserum to IL-6 (but not an antiserum to IL-1 beta) neutralized the activity of the monocyte supernatant and blocked T cell proliferation. An anti-IL-2R antibody also completely inhibited T cell proliferation induced by the combination of mAb 9.3, IL-2, and IL-6. Our results provide evidence that cross-linking of CD28 induces functional IL-2R and that this activity is dependent on a helper signal provided by monocytes, more specifically IL-6. Moreover, our results indicate that IL-6 (previously called B cell stimulatory factor-2) is active on T cells. If a natural ligand for CD28 can be identified, the mechanism of induction of IL-2 responsiveness described here might explain how T cells become nonspecifically involved in an ongoing cellular immune reaction.

Adjuvants, Immunologic↗
PubMed1988

A novel, NH2-terminal sequence-characterized human monokine possessing neutrophil chemotactic, skin-reactive, and granulocytosis-promoting activity.

A factor able to induce an early local inflammation in rabbit skin was detected in the supernatant of mitogen-stimulated human blood leukocytes. The factor was different from IL-1 which, although present in the supernatants, was chemically separable from the factor and induced a late rather than an early skin response. Other biological effects of the principal factor were its in vitro chemotactic effects on granulocytes and its ability to induce rapid granulocytosis upon intravenous injection in rabbits. When tested under the same conditions, IL-1 beta did not act chemotactically and induced granulocytosis at a later time. The factor was purified to homogeneity and identified by electrophoretic mobility as a protein of Mr 6,500. Amino acid sequence analysis revealed the presence of an uncontaminated NH2-terminal sequence identical to a segment of the sequence previously predicted from the cDNA clone (3-10C) copied from an mRNA isolated from human leukocytes and coding for a protein of unknown function. The NH2-terminal sequence of the factor also showed extensive homology to that of the platelet factors beta-thromboglobulin (beta TG) and platelet factor 4 (PF-4). Studies done to identify the cell source of the factor revealed that it was produced by adherent mononuclear cells but not by platelets, while the opposite was true for beta TG.

Amino Acid Sequence↗
PubMed1988

Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma.

Acute experimental allergic encephalomyelitis (EAE) was induced in C57BL/6J and SJL/J mice by injection of isologous spinal cord homogenate given in conjunction with Bordetella pertussis and Freund's adjuvant. SJL/J mice showed a highly aggressive and 100% lethal form of the disease; C57BL/6J mice were much less susceptible as they had low morbidity rates (20 to 40%), low disease scores, and mostly no mortality. Treatment of these low susceptibility mice with neutralizing mAb against IFN-gamma caused an increase in morbidity rates as well as significant mortality (up to 80%). Similar antibody treatment did not affect the course of the disease in the high susceptibility SJL/J mice. However, treatment of these mice with IFN-gamma resulted in reduced morbidity and mortality. A similar but less pronounced inhibition of the disease in SJL/J mice could be obtained by administration of IFN-alpha/beta or by acute infection with lactate dehydrogenase virus. The results indicate that endogenous as well as exogenous IFN can exert a down-regulating effect on the development of EAE. They also indicate that endogenous IFN-gamma is produced during the development of EAE and plays a disease-limiting role.

Adjuvants, Immunologic↗
PubMed1988

Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6.

Supernatants of mitogen-stimulated human leukocytes contain two biologically related cytokines, IL-1 and hybridoma growth factor (HGF). IL-1 beta is a potent inducer of HGF in fibroblasts but has little stimulating effect on monocytes that spontaneously produce HGF. Leukocyte-derived HGF and IL-1 were separated by the use of affinity chromatography on specific antibodies and discriminating assay systems for both cytokines. They had different Mr upon gel filtration and SDS-PAGE. In contrast to IL-1 beta, HGF showed heterogeneity on a cation-exchange column. IL-1 beta and HGF were purified to homogeneity by a sequence of four and five purification steps, respectively. Leukocyte-derived HGF was characterized by analysis of its NH2-terminal amino acid sequence. This revealed complete homology with fibroblast-derived HGF, 26-kDa protein, IFN-beta 2, and B cell stimulatory factor 2, molecules which have collectively been designated as IL-6. IL-1 beta exerted an antiviral and growth-promoting effect of fibroblasts, whereas HGF/IL-6 did not. Both IL-1 and IL-6 possessed lymphocyte-activating factor activity, which could be neutralized only by an anti-serum against the corresponding cytokine.

Amino Acid Sequence↗
PubMed1988

Interleukin-1 stimulates steroidogenesis in cultured rat Leydig cells.

We have studied the effects of human interleukin-1 beta on steroidogenesis in cultured immature rat Leydig cells. In the presence of low concentrations of LH or in its absence interleukin-1 beta markedly stimulates the production of C19-steroids (testosterone and androstenedione) and C21-steroids (progesterone, 17 alpha-hydroxyprogesterone, 20 alpha-hydroxypregn-4-en-3-one). In the presence of maximally effective concentrations of LH, on the contrary, interleukin-1 beta inhibits C19-steroid production by provoking a block at the level of the 17,20-desmolase. These actions were observed with similar low doses of interleukin-1 beta (ED50 = 1 U/ml), but the stimulatory effects are evident within the first 2 h of incubation whereas the inhibitory actions appeared after a latent period of 6 h. None of the effects of interleukin-1 beta is accompanied by measurable changes in cAMP output, and the effects are much less pronounced in freshly isolated Leydig cells than in cultured cells. At maximally effective doses the effects of interleukin-1 beta are additive with those of a number of other Leydig cell agonists: LHRH, epidermal growth factor, arginine vasopressin and Sertoli cell-derived factor(s), suggesting that these agonists act by mechanisms different from that of interleukin-1 beta. The possibility is considered that Leydig cells may act as target cells for interleukin-1 beta derived from testicular macrophages or for interleukin-1-like factors derived from testicular tubules.

17-alpha-Hydroxyprogesterone↗