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N Haeffner-Cavaillon

Publications and source records attributed to N Haeffner-Cavaillon.

87 records · Page 5Linked to original sources
PubMed1986

Polymyxin-B inhibition of LPS-induced interleukin-1 secretion by human monocytes is dependent upon the LPS origin.

Polymyxin-B (PMB) is an antibiotic known to inhibit various biological activities induced by lipopolysaccharides (LPS). We have investigated the ability of PMB to inhibit LPS-induced interleukin-1 (IL-1) secretion by human monocytes in vitro. Interleukin-1 was assayed by the conventional comitogenic assay using mice thymocytes. Our data demonstrate that PMB (1-2 micrograms/assay)-mediated inhibition of LPS-induced IL-1 secretion depends on the origin of the LPS. Interleukin-1 secretions induced by Escherichia coli and Acinetobacter calcoaceticus LPSs, when used at 1 microgram/assay were completely inhibited by PMB, whereas those induced by Neisseria gonorrheae, Neisseria meningitidis, Bordetella pertussis, and Salmonella enteritidis LPSs were unaffected. Neisseria meningitidis, the most potent IL-1 inducer tested could be inhibited by PMB only at concns below 5 ng/assay; when the assay was performed in the presence of serum (0.2%) PMB could not completely inhibit Neisseria meningitidis LPS-induced IL-1 secretion at LPS doses as low as 100 pg/assay. Polymyxin B itself, at doses greater than 50 micrograms/assay, stimulated IL-1 secretion and acted synergistically with LPS to induce IL-1 secretion when used at 10 micrograms/assay. Potential relevance of Lipid A-mediated IL-1 secretion and the use of PMB to detect endotoxin contamination is discussed.

Blood↗
PubMed1986

Inability of pyrogenic, purified Bordetella pertussis lipid A to induce interleukin-1 release by human monocytes.

Free lipid A of Bordetella pertussis, Neisseria meningitidis, and Escherichia coli lipopolysaccharide (LPS) was prepared by hydrolysis in acetate buffer (pH 4.5); in addition, lipid A from B. pertussis and E. coli was prepared by hydrolysis in mineral acid (HCl). The precipitates obtained were purified by extraction methods in toluene-methanol and are referred to as crude lipid A. Purified lipid A from N. meningitidis and B. pertussis was obtained by extraction in a mixture of chloroform-methanol-water-triethylamine. The different preparations were tested for their pyrogenicity (endogenous pyrogen; EP) and their capacity to trigger the release of interleukin-1 (IL-1; previously known as lymphocyte-activating factor; LAF) by human monocytes. Crude lipid A from E. coli and N. meningitidis were both IL-1 inducers. Crude B. pertussis lipid A (acetate buffer; pH 4.5), which contains a beta-1-6-linked D-glucosamine disaccharide, two phosphoryl groups, and five fatty acids, was pyrogenic and an IL-1 inducer (EP+/LAF+); but crude B. pertussis lipid A (0.25 N HCl), which lacked the glycosidic phosphoryl group, was 1,000-fold less pyrogenic than the diphosphorylated lipid A, yet it retained its IL-1-inducing capacity (EP-/LAF+). Purified N. meningitidis lipid A was not an inducer of IL-1 release and purified B. pertussis lipid A exhibited identical pyrogenicity as the parent LPS but was devoid of any IL-1-release inducing capacity (EP+/LAF-). These results demonstrate that for some endotoxins, purified lipid A is unable to induce IL-1 release by human monocytes; however, it is pyrogenic, supporting the hypothesis that IL-1 and EP are induced by different determinants on the LPS molecule.

Bordetella pertussis↗
PubMed1985

Specific binding of endotoxin to human monocytes and mouse macrophages: serum requirement.

Specific binding of Bordetella pertussis and Neisseria meningitidis endotoxins to human monocytes and murine macrophages was demonstrated. Binding of B. pertussis endotoxin could be inhibited by endotoxins of Salmonella minnesota, Escherichia coli, and Klebsiella pneumoniae, the extent of inhibition being dependent on the origin of the lipopolysaccharides and on the origin of the mononuclear phagocytic cells. The binding of B. pertussis and N. meningitidis endotoxins which was mediated by the polysaccharide region of the endotoxins was serum dependent. The results indicated that the binding of endotoxin was promoted neither by natural antibodies directed against the endotoxin nor by proteins known to combine with endotoxins: immunoglobulins, albumin, or fibronectin; we have provided some evidence that complement components may play a role in the specific binding of endotoxins to the monocyte/macrophage membrane.

Animals↗
PubMed1985

The role of serum in interleukin 1 production by human monocytes activated by endotoxins and their polysaccharide moieties.

Lipopolysaccharides (LPS) as well as polysaccharide (PS) moieties of Bordetella pertussis and Neisseria meningitidis endotoxins induced in vitro interleukin 1 (IL 1) secretion by human monocytes as evaluated by the co-mitogenic assay on C3H/HeJ thymocytes. Because of the role of serum in the specific binding of endotoxins to monocytes mediated by the polysaccharide region [12], experiments were undertaken to study the effect of serum on IL 1 induction. Although the presence of serum is not necessary for the secretion of IL 1 by monocytes stimulated by LPS or PS, the addition of very small amounts of human serum (0.1-1.6%) to the cultures of human adherent cells potentiated the IL 1 secretion, without modifying the background values. Natural anti-B. pertussis antibodies present in the serum were not responsible for the observed phenomenon. Heating at 56 degrees C for 30 min did not alter the enhancing effect. The data presented suggest that the serum component(s) and the IL 1 inducers (LPS or PS) act in synergism by two different pathways since the two signals can be delivered sequentially.

Antibodies, Bacterial↗
PubMed1984

Interleukin 1 secretion by human monocytes stimulated by the isolated polysaccharide region of the Bordetella pertussis endotoxin.

The isolated polysaccharide chain, PS-1, of the Bordetella pertussis endotoxin was examined by isoelectric focusing, SDS-polyacrylamide gel electrophoresis and gel filtration for heterogeneity and for possible contamination by the parent endotoxin. This polysaccharide, previously found to be a very potent, macrophage-dependent, polyclonal B-cell activator and to mediate the specific binding of the endotoxin to macrophages, stimulated the interleukin 1 (IL 1) secretion by human monocytes; its potency was similar to that measured for the endotoxin. It was concluded that endotoxin-induced IL 1 production may be initiated by the interaction of the polysaccharide chain of the B. pertussis endotoxin and a specific structure present on macrophages.

Adult↗
PubMed1982

Lipopolysaccharide receptor on rabbit peritoneal macrophages. I. Binding characteristics.

The Bordetella pertussis endotoxin, labeled with tritium ((3H)-LPS), bound irreversibly and nonspecifically to rabbit lung macrophages, but bound reversibly and specifically to both resident and elicited rabbit peritoneal macrophages. The specific binding capacity of the macrophages was saturated with about 3 X 10(4) LPS molecules per cell. The binding was inhibited with the homologous unlabeled endotoxin, but not at all with endotoxin from Proteus mirabilis, thus assessing ligand specificity. Endotoxins from other bacteria gave intermediate inhibition value. Binding of tritium-labeled pertussis endotoxin was significantly inhibited by one of the two polysaccharides (PS-1) present in this endotoxin, but neither the other polysaccharide (PS-2) nor the Lipid A fragment exhibited such activity. These results strongly suggest the presence of a lectin-like receptor for LPS on the membrane of rabbit peritoneal macrophages.

Animals↗
PubMed1981

Expression of biological effector functions by immunoglobulin G molecules lacking the hinge region.

Several biological effector functions mediated by sites on the Fc region of human IgG1 have been studied in two variant IgG1 kappa monoclonal proteins (Dob and Lec) which contain deletions corresponding to the entire hinge region of the heavy chains. Neither Dob nor Lec protein in aggregated form was able to activate the classical complement pathway, and this was shown to be due to an inability to bind the first component of complement (C1). By rosette inhibition assays, Dob and Lec proteins were shown to have no measurable affinity for Fc receptors on human B cells or neutrophils. Dob and Lec proteins had a much reduced affinity for Fc receptors on the murine macrophage-like cell line P388D1 when compared to normal human IgG1. Furthermore, the hinge-deleted proteins were able to compete with murine IgG2b for P388D1 receptors but not with murine IgG2a. In contrast, the binding of Dob and Lec proteins to protein A from Staphylococcus aureus was entirely normal. The functional consequences of the hinge deletion were parallel to those seen when normal IgG1 was reduced and alkylated. It was concluded that the functional impotency of Dob and Lec proteins was related to the close association between the Fab and Fc regions in these molecules and the limited degree of segmental flexibility permitted in the absence of the hinge region. The data also suggest a major role for the C gamma 2 domain (C is the constant region) in mediating effector functions in normal IgG1.

Animals↗
PubMed1980

Biological activities of fragments derived from Bordetella pertussis endotoxin: isolation of a nontoxic, Shwartzman-negative lipid A possessing high adjuvant properties.

Endotoxin from fresly sedimented Bordetella pertussis cells, isolated by the phenol/water procedure when submitted to kinetically controlled, mild acidic hydrolysis released a polysaccharide (polysaccharide 1), a complex lipid (lipid X), and a glycolipid. When treated with somewhat stronger acid, the glycolipid yielded a second polysaccharide (polysaccharide 2) and another complex lipid (lipid A). The intact pertussis endotoxin had all the usual properties of endotoxins extracted from enteric bacteria. Lipid X and the intermediary glycolipid retained all the endotoxic properties of the unfractionated endotoxin. In lipid A, pyrogenicity was reduced to a very low level and toxicity and Shwartzman reactivity were absent; however, this fraction retained most of the endotoxin's antiviral activity, and its adjuvant power was considerably higher than that of the intact endotoxin. Lipid A elicited nonspecific resistance against challenge with certain bacteria, but not against others.

Adjuvants, Immunologic↗
PubMed1979

Studies on the Fc gamma receptor of the murine macrophage-like cell line P388D1. II. Binding of human IgG subclass proteins and their proteolytic fragments.

Binding studies of human IgG proteins to murine P388D1 cells indicated that they bind to an apparently homogeneous Fc receptor population. The association constant was 0.89 x 10(6)M-1 at 22 degrees C and was comparable to the binding affinities of homologous murine IgG2a and IgG2b. The number of receptor sites was found to be approximately 6 x 10(5)/cell. Fc gamma 1 and Fc gamma 3 fragments bound with an affinity comparable to that of the parent proteins. The P388D1 receptors could discriminate between the human IgG subclasses; the relative cytophilic activity was IgG3 greater than IgG1 greater than IgG4 and IgG2 was devoid of binding activity. Fragments corresponding to the C gamma 2 and C gamma 3 domains of human IgG1 were both unable to bind to the P388D1 receptors either alone or in equimolar combination. This suggests that the cytophilic site may be formed cooperatively by interaction between the two domains. The integrity of the hinge region appeared to be essential for full expression of cytophilic activity since reduction of the hinge-region disulfides in both human IgG1 and its Fc fragment markedly decreased their binding affinity. In addition, a mutant IgG1 molecule lacking the hinge region was significantly less cytophilic than its normal counterpart.

Animals↗
PubMed1979

Rabbit B spleen lymphocytes and T helper cells. I. Responsiveness to mitogens of B cell subpopulations of different sedimentation velocities and subpopulations bearing or lacking Fcgamma receptors.

The response to anti-allotype (anti-Ab4), Nocardia Water Soluble Mitogen (NWSM), pneumococcal polysaccharide type III (SSS III), and human Fc fragments of various purified and unfractionated rabbit spleen cell populations was determined in terms of 3H-thymidine up-take. B cells were isolated either from untreated suspensions of spleen cells or from suspensions from which adherent and phagocytic cells were removed. The purification factor was greater than the enhancement of 3H-thymidine uptake by anti-Ab4, NWSM, and SSS III as compared with the response of unfractionated spleen cells. It thus appears that a helper cell was involved: the mitogen response of purified B cells was enhanced by the addition of T cells. B subpopulations were separated by sedimentation or by rosetting, which allowed us to separate Fcgamma receptor-bearing cells from cells that did not possess this receptor. There were differences between cells responding to B mitogens not only in sedimentation velocity but also in the absolute number of cells. B cells bearing the Fcgamma receptor were less responsive to anti-Ab4 and more responsive to SSS III, NWSM, and human Fc than were B cells lacking the Fcgamma receptor.

Animals↗