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J M Cavaillon

Publications and source records attributed to J M Cavaillon.

At least 91 records · Page 5Linked to original sources
PubMed1989

In vivo induction of interleukin-1 during hemodialysis.

In vivo induction of interleukin-1 (IL-1) production during hemodialysis was investigated by measuring IL-1 activity in monocyte lysates from 59 patients undergoing long-term maintenance hemodialysis with complement activating and non-complement activating devices. In patients dialyzed with new hollow-fiber cuprophane dialyzers, predialytic (T0) monocyte-associated IL-1 activity was 12.5 +/- 3.0 U/ml (mean +/- SEM), a value that was higher than that found in normal individuals (2.85 +/- 0.85 U/ml; P less than 0.0025) and in non-dialyzed patients with chronic renal failure (0.95 +/- 0.85 U/ml, P less than 0.0001). Cell-associated IL-1 activity was consistently increased after five hours of dialysis with cuprophane membranes (42.4 +/- 5.5 U/ml, P less than 0.0005). Systemic complement activation was demonstrated by the finding of increased plasma levels of C3adesArg antigen during dialysis. In patients dialyzed with high permeability polyacrylonitrile and polysulfone membranes, no intradialytic change in cell-associated IL-1 and no complement activation occurred. However, the mean predialytic values of monocyte-associated IL-1 in these patients (that is, 32.9 +/- 5.6 U/ml and 38 +/- 5.65 U/ml for the polyacrylonitrile and the polysulfone groups, respectively) were higher than the predialytic levels of cell-associated IL-1 in the patients from the cuprophane group (P less than 0.0025). Monocytes obtained at the beginning and five hours of dialysis from patients dialyzed with polyacrylonitrile devices, and monocytes obtained at five hours but not at the beginning of dialysis from patients dialyzed with cuprophane membranes, spontaneously released extracellular IL-1 after 24 hours of culture in serum free conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Dissociation of cell-associated interleukin-1 (IL-1) and IL-1 release induced by lipopolysaccharide and lipid A.

The capacities of lipopolysaccharide (LPS) and lipid A to trigger mouse BALB/c peritoneal macrophages and to induce the production of cell-associated interleukin-1 (IL-1) and membrane-associated IL-1 and IL-1 release have been compared. Bordetella pertussis lipid A was 1,000 to 10,000 times less efficient than the native LPS to induce IL-1 release by freshly isolated elicited macrophages. When resident macrophages were studied, lipid A, at high concentrations (greater than 2 micrograms/ml), induced significant levels of cell-associated IL-1 but little or no IL-1 release. With synthetic lipid A built up with the Escherichia coli lipid A structure (compound 506), IL-1 activity was present in the supernatants of elicited peritoneal macrophages and to a lesser extent in those of resident macrophages. However, the release of IL-1 induced by synthetic lipid A 506 remained much lower than those induced by rough LPS. Membrane-associated IL-1 could be induced on BALB/c macrophages with LPS and natural or synthetic lipid A, the LPS being the most active. In C3H/HeJ mice, neither natural nor synthetic lipid A could induce detectable cell-associated IL-1, whereas LPS could induce cell-associated and membrane IL-1 activity but no IL-1 release. Our results indicate that fragments of endotoxins may induce the production of IL-1 but the entire structure of the LPS molecule is the most effective to induce intracellular IL-1 production, expression of membrane IL-1, and release of IL-1.

Animals↗
PubMed1988

A sensitive, IL-2-independent, assay for IL-1.

The thymocyte costimulator (LAF) assay, the standard biological test used for IL-1 titration, has a low sensitivity and lacks specificity since it can be potentiated by the IL-2 which is frequently present in IL-1-containing biological fluids. We describe here a new IL-1 titration method which takes advantage of the capacity of a thymoma line, EL4-6.1, to differentiate and express IL-2 receptors upon stimulation by IL-1 in the presence of a suboptimal dose of phorbol diester. Membrane IL-2R measurement on this indicator cell line permits the detection of 1-2 X 10(-4) ng/ml IL-1, compared to 5 X 10(-2) ng/ml in the LAF assay. In addition, rIL-2 up to 250 U/ml has no effect on IL-1 measurement by this assay, which also exhibits a 100-fold lower sensitivity to inhibitory effects of prostaglandin, compared to the LAF assay. Finally, tumor necrosis factor alpha only exerts a weak costimulation effect at very high doses. A flow cytometry technique and an ELISA are described for IL-2 receptor detection. Due to its high sensitivity and specificity, this novel assay should now permit reliable IL-1 titration in biological fluids such as IL-2-rich lymphocyte culture supernatants.

Animals↗
PubMed1988

Lymphocyte proliferative responses to the purified Dermatophagoides farinae major allergen in untreated and hyposensitized atopic patients.

We investigated the proliferative response of lymphocytes from mite-sensitive patients (RAST D.far greater than 3.5 PRU/ml) in the presence of the major allergen Der.f.I purified from Dermatophagoides farinae. Comparative studies were carried out with peripheral blood mononuclear cells from non-atopic donors (RAST = 0), and from patients undergoing hyposensitization treatment (5 to 24 months). According to Student's t-test, there was no significant difference in the Der.f.I-induced proliferation of peripheral blood mononuclear cells from normal donors, untreated atopic patients and hyposensitized patients. In conclusion, it was impossible to discriminate between normal donors, atopic patients and hyposensitized patients with regard to their circulating lymphocyte responses to the purified major allergen Der.f.I.

Allergens↗
PubMed1987

C3a(C3adesArg) induces production and release of interleukin 1 by cultured human monocytes.

Purified human C3a(C3adesArg) induced dose-dependent generation of intracellular IL 1 activity and release of IL 1 in cultures of human mononuclear adherent cells in serum-free conditions. Concentrations of C3a(C3adesArg) of 10(-8) M and 6 hr of culture were sufficient to induce production of cell-associated IL 1, as detected in monocyte lysates. Ten- to 100-fold higher concentrations of C3a(C3adesArg) and 24 hr of culture were required for induction of IL 1 release. Release of IL 1 induced by suboptimal amounts of C3a(C3adesArg) was greatly enhanced by the addition of indomethacin to the culture medium. Contamination with C5a of the C3a(C3adesArg) preparation did not account for C3a(C3adesArg)-induced IL 1 production. Induction of IL 1 activity by C3a(C3adesArg) was not due to contaminating LPS, as indicated by the following observations: the amount of contaminating LPS in C3a(C3adesArg) was below that which could induce IL 1 release from human monocytes in serum-free conditions; induction of IL 1 by C3a(C3adesArg) was not suppressed by polymyxin B; kinetics of IL 1 production and release in the presence of C3a(C3adesArg) differed from those observed in the presence of LPS; and sialated gangliosides, which inhibit IL 1 release induced by LPS, had no effect on the induction of IL 1 by C3a(C3adesArg). The C3a(C3adesArg) preparation used in this study mostly contained the desArg derivative, suggesting that, in contrast with the requirement for an intact C-terminal arginyl residue for the spasmogenic activity of C3a, both C3a and its C3adesArg derivative may interact with receptors on human monocytes. By inducing IL 1 production and release, C3a(C3adesArg) may contribute to the generation of the inflammatory process and the regulation of the immune response.

Cells, Cultured↗
PubMed1987

Inhibition by gangliosides of the specific binding of lipopolysaccharide (LPS) to human monocytes prevents LPS-induced interleukin-1 production.

In a previous work we have reported that gangliosides inhibit interleukin 1 (IL-1) release by human monocytes stimulated with lipopolysaccharides (LPS). In the present study we extend this work to IL-1 production and we correlate these observations with the capacity of gangliosides to inhibit the binding of radiolabeled LPS to its specific receptor on human monocytes. Preincubation of 3H-LPS with crude bovine brain gangliosides, as well as purified human brain mono, di, and trisialogangliosides (GM1, GD1a, and GT1b, respectively), led to an inhibition of the specific binding of LPS to the cell surface. Neither ceramide nor N-acetyl neuraminic acid, two constituents of gangliosides, was able by itself to inhibit the specific binding. A strict parallelism was observed with respect to inhibition on LPS-induced IL-1 production and release. Asialoganglioside (asialo-GM1) was inactive in both assays, suggesting that the N-acetyl neuraminic acid plays a role within the ganglioside molecule, with respect to inhibitory activity. We conclude that LPS-induced production and release by human monocytes is not due to a signal triggered by nonspecific absorption and/or intercalation of LPS into cell membrane which occur through hydrophobic interaction mediated by the lipid A region. Addition of exogenous sialogangliosides which blocked LPS-induced IL-1 production and release, did not modify significantly the nonspecific binding of 3H-LPS, whereas it did inhibit the specific binding which is mediated by the polysaccharide moiety of the LPS molecule. These results establish a relationship between the specific endotoxin receptor on monocytes and a LPS-induced cellular function.

Binding, Competitive↗
PubMed1986

Presence of interleukin 3-like activity in the supernatants of lipopolysaccharide-stimulated mouse splenocytes.

An Interleukin 3 (IL 3) activity was found in the supernatants of mouse spleen cells stimulated by lipopolysaccharide (LPS). The IL 3 activity was maximum in the supernatants of 5 to 7 days cultures. IL 3 activity was assessed by the capacity of the spleen cell supernatants to allow the growth of the FDC-P2 cell line, a strictly IL 3 dependent cell line. Polymyxin B could inhibit the IL 3 induction by LPS.

Animals↗
PubMed1986

Molecular requirement for interleukin 1 induction by lipopolysaccharide-stimulated human monocytes: involvement of the heptosyl-2-keto-3-deoxyoctulosonate region.

Experiments were undertaken to localize in the lipopolysaccharide (LPS) the minimal structural determinants sufficient to initiate the signal leading to interleukin 1 (IL 1) secretion by human monocytes. Our results clearly demonstrated that this signal is triggered by structures present in the so-called inner-core region which chemically consists of 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) and heptose in many LPS of gram-negative bacteria. Thus, the isolated polysaccharide region of Bordetella pertussis endotoxin as well as fragments derived therefrom containing the reducing KDO unit were able to induce similar levels of IL1 induction as the native LPS. Similarly, the trisaccharide alpha-D-manno-heptopyranosyl-(1-3)-alpha-D-manno-heptopyranosyl -(1-5)-3 -deoxy-D-manno-octulosonic acid (hep-hep-KDO), representative for the inner-core region of a large number of enterobacterial LPS, was a very potent IL 1 inducer. Neither KDO monosaccharide, nor the alpha-(2-4)-linked 3-deoxy-D-manno-octulosonic acid disaccharide isolated from Salmonella rough-form LPS promoted the signal indicating that the minimal structure of endotoxin able to induce IL 1 secretion resides in the hep (1-5)-KDO disaccharide.

Carbohydrate Sequence↗
PubMed1986

Inhibition of lipopolysaccharide-induced monocyte interleukin 1 secretion by gangliosides.

Gangliosides known to be potent immunosuppressors are shown to inhibit the secretion of interleukin 1 (IL 1) by human monocytes stimulated with lipopolysaccharide (LPS). The inhibitory activity was observed either with mono-, di- or trisialogangliosides. The inhibition of LPS-induced IL 1 secretion was obtained in the presence of indomethacin, indicating that the ganglioside inhibitory capacity was not due to prostaglandin induction. Indeed the inhibitory activity seems to be mediated by an interaction with LPS molecules, preventing their ability to deliver a signal to monocytes for IL 1 secretion.

Gangliosides↗
PubMed1986

Ganglioside identification on human monocyte membrane with Clostridium perfringens delta-toxin.

Clostridium perfringens delta-toxin was first described as a hemolysin with a restricted lytic spectrum. A selective cytotoxicity of the delta-toxin was then found on rabbit leukocytes: peritoneal and alveolar macrophages were uniformly killed, whereas thymocytes were essentially resistant. The toxin was shown to be specific for GM2 ganglioside or a GM2-like structure. In the present study we report the interaction of delta-toxin with human monocytes. A specific, saturable, and irreversible binding of 125I-delta-toxin was demonstrated. Binding was inhibited by preincubation of the radiolabeled toxin with GM2 and with high amount of GM1 ganglioside. As judged by dye exclusion, no cytotoxicity was observed on freshly isolated monocytes, but when added at the beginning of a culture of human adherent cells, the cytotoxic effect was detected after 48 hours of culture. Taken together, these data indicate the presence of monosialoganglioside(s) at the surface of human monocytes, and suggest a possible reorganisation of such structure into the cell membrane when monocytes mature in vitro toward macrophage-like cells.

Bacterial Toxins↗
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↗