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N Haeffner-Cavaillon

Publications and source records attributed to N Haeffner-Cavaillon.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Cytokines and inflammation].

Numerous cytokines are present in inflammatory foci. Two of them, interleukin-1 (IL-1) and tumour necrosis factor (TNF), play a major role in coordinating mechanisms which command inflammation. Under their action many cells produce lipidic mediators, proteolytic enzymes or free radicals, all factors that are directly responsible for the noxious effects observed. IL-1 and/or TNF exert cytotoxic activities on vascular epithelium, cartilage, bone, muscle or beta cells of pancreatic islets. Such cytokines as interferon gamma (IFN gamma), IL-3 or granulocyte-macrophage colony stimulating factor (GM-CSF) amplify the inflammatory response by increasing the production of IL-1 and TNF by macrophages. GM-CSF also produces other cytokines, such as IL-8 and the macrophage chemoattractant protein 1 (MCP-1), the chemotactic properties of which participate in the recruitment of leucocytes within the focus of inflammation. IL-6 abounds in inflammatory processes and induces the production by hepatocytes of acute inflammation phase proteins. The same applies to IL-1, TNF, IL-11, the leukaemia inhibitory factor (LIF) or the transforming growth factor beta (TGF beta). The latter also possesses a number of anti-inflammatory activities and, like IL-4 and IL-10, can inhibit IL-1 and TNF production. Glucocorticoids have this potential activity, and they may be produced by a cascade of events initiated by IL-1, TNF and IL-6, involving the neuroendocrine system. The concept of "cytokine network", therefore, perfectly illustrates the participation of these mediators in inflammatory mechanisms.

Cytokines↗
PubMed1993

Complement activation and cytokine production as consequences of immunological bioincompatibility of extracorporeal circuits.

The use of devices which result in exposure of blood to artificial surface has gained increasing importance in routine medical and surgical practice. In the field of biocompatibility, attention has long been directed at the mechanisms of thrombus formation of surfaces. In recent years however, a special interest has emerged for the study of the immunological consequences of blood-artificial surface interactions, thus broadening the concept of hemocompatibility. The contact of blood with artificial devices results in the activation of a number of humoral and cellular processes involved in natural and in specific immunological recognition of foreign surfaces by the host, and in the secondary occurrence of acute and chronic adverse reactions in patients undergoing extracorporeal circulation. The purpose of this review is to discuss the mechanisms involved in immunological bioincompatibility of extracorporeal circuits, with particular emphasis on the molecular basis of the activation of the complement system, the role of endotoxins, and the induction of cytokine production by activated monocytes.

Biocompatible Materials↗
PubMed1993

Complement activation by gp160 glycoprotein of HIV-1.

The ability of the gp160 envelope glycoprotein of HIV-1 to activate human complement and to bind C3 fragments was investigated by incubating mammalian-derived recombinant gp160 with seronegative serum and by quantitating the binding of C3b/iC3b to the protein using a biotinylated monoclonal antibody directed against a neoepitope expressed by cleaved human C3. Recombinant gp160 activated complement in a dose- and time-dependent fashion. Complement activation occurred through the classical pathway, independently of antibodies, and required C1q. Binding of anti-HIV IgG to rgp160 prior to exposure of the envelope glycoprotein to serum resulted in enhanced complement activation. Complexes of rgp120 with anti-HIV IgG also cleaved C3 in serum, resulting in deposition of C3b on gp120. These results provide a basis for C3-mediated facilitation of viral entry into target cells expressing receptors for fragments of human C3.

Antibody Specificity↗
PubMed1993

CR1 (CD35) and CR3 (CD11b/CD18) mediate infection of human monocytes and monocytic cell lines with complement-opsonized HIV independently of CD4.

Peripheral blood and tissue mononuclear phagocytes serve as major viral reservoirs in HIV-infected individuals. We investigated the role of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) in mediating productive infection with complement-opsonized HIV-1 and HIV-2 of cultured normal human peripheral blood monocytes, the promonocytic cell line THP-1, the monocytic cell line Mono Mac 6 and the glial cell line U251-MG. Cells were infected with the HTLV-IIIB strain of HIV-1 or the LAV-2 strain of HIV-2 that had been preopsonized with fresh human normal HIV seronegative serum. Productive infection was assessed by syncytia formation, the MTT cytotoxicity assay and/or release of p24 antigen in culture supernatants. Using suboptimal amounts of virus to infect the cells, we observed a higher and earlier productive infection of the cells with complement-opsonized HIV than with unopsonized virus. The enhancing effect of complement was totally suppressed by blocking CR1 or CR3 function with F(ab)'2 fragments of anti-receptor MoAbs; while blocking of the LFA-1 antigen had no effect. The infection of monocytic cells with complement-opsonized virus occurred independently of CD4 since it was not inhibited by F(ab)'2 fragments of a MoAb against the gp120 binding site of CD4 and since infection also occurred with Mono Mac 6 and U251-MG cells, which lack expression of the CD4 antigen and of CD4 mRNA. These observations suggest that complement may mediate productive infection of cells of the monocytic lineage with 'lymphocytotropic' HIV strains independently of CD4.

Antigens, CD↗
PubMed1992

Membrane molecules which trigger the production of interleukin-1 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated human monocytes.

We have investigated the role of the membrane molecules CD11/CD18 and CD14 which may mediate the binding of lipopolysaccharide (LPS) to human monocytes, in the induction of the production and release of interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) by LPS-stimulated cells. Blockade of CD11a, CD11b and CD18 with saturating concentrations of specific mAb did not inhibit the release of cytokines from LPS-stimulated monocytes. In contrast, inhibition of the release of IL-1 beta and TNF-alpha occurred in monocytes cultures that had been pretreated with either of two monoclonal antibodies (mAb) recognizing different epitopes on the CD14 molecule. The binding of LPS to CD14 has been previously shown to require serum factors. In the present study, we found that serum had an enhancing effect on the release of IL-1 and TNF-alpha from LPS-stimulated cultures of normal human monocytes. The inhibitory effect of anti-CD14 mAb was, however, observed in cultures performed in the presence or in the absence of serum, suggesting that triggering of IL-1/TNF-alpha release by CD14 is independent of LPS-binding proteins or other serum proteins. IL-1 beta and TNF-alpha were also released from LPS-stimulated cultures of monocytes from patients with paroxysmal nocturnal hemoglobinuria lacking expression of CD14. Thus, CD14 but not CD11/CD18 can trigger serum-dependent and independent cytokine release from endotoxin-stimulated normal human monocytes; CD14 is not, however, the only LPS receptor that is involved in the secretory response of endotoxin-stimulated cells.

Antibodies, Monoclonal↗
PubMed1992

Decreased expression of the membrane inhibitor of complement-mediated cytolysis CD59 on T-lymphocytes of HIV-infected patients.

OBJECTIVE: To study the expression of the membrane inhibitor of complement-mediated cytolysis, CD59, on peripheral blood mononuclear cells (PBMC) from HIV-infected individuals. METHODS: CD59 membrane expression was investigated by double immunofluorescent staining on purified PBMC from HIV-infected patients and seronegative controls. RESULTS: CD59 expression was decreased on peripheral blood T-lymphocytes from HIV-infected patients. Decreased expression of CD59 antigen did not correlate with clinical stage of disease. Low CD59 expression on T-lymphocytes was mediated by several mechanisms, including: (1) decrease in number of CD4+ cells which normally express high amounts of the antigen; (2) relative increase in CD8+ cells, more specifically in CD8+ CD57+ cells expressing a low density of the antigen; (3) loss of or decreased CD59 expression on a subpopulation of CD3+ belonging either to the CD4+ or to the CD8+ subset. Decreased CD59 expression was consistently observed on CD8+ lymphocytes. CD59 expression was normal on patient red blood cells, monocytes and B-lymphocytes. CONCLUSIONS: HIV infection is associated with a T-cell-specific defect in CD59 membrane expression. Decreased CD59 expression may result in increased susceptibility of T-lymphocytes from HIV-infected patients to complement-mediated lysis.

Antigens, CD↗
PubMed1991

Binding sites for endotoxins (lipopolysaccharides) on human monocytes.

The nature of the binding sites for LPS on human monocytes was investigated using [3H] labeled intact LPS from Neisseria meningitidis and from Salmonella minnesota R7, and the [3H] labeled purified inner core region (PS-OMe) of S.m. R7 LPS. In the presence of serum, intact LPS from enterobacterial and nonenterobacterial strains bound to monocytes in a dose-dependent, saturable, and displaceable fashion. N.m. LPS and LPS from the enterobacterial strain of Escherichia coli 0111-B4 bound to the same sites on monocytes as assessed in competitive binding experiments. Specific binding of intact LPS to monocytes occurred through the CD14 molecule as shown by the ability of mAb and of F(ab')2 fragments of mAb directed against specific epitopes of CD14 to inhibit the binding of [3H]-LPS to cells and by the lack of binding of intact LPS to CD14-deficient cells from patients with paroxysmal nocturnal hemoglobinuria. Specific binding of LPS to monocytes was not mediated by the CD11/CD18 complex because mAb to the alpha and beta chains of the Leu-CAM molecules did not alter the binding of LPS to cells and because LPS did not inhibit the binding of labeled mAb to monocytes. [3H]-PS-OMe also bound in a dose-dependent and displaceable fashion to monocytes involving an unidentified, non-CD14, binding site on the cells. Binding of LPS to monocytes also involved nonsaturable binding sites for hydrophobic structures of LPS as evidenced in binding experiments performed in the absence of serum. These observations indicate that intact LPS may interact with the monocyte membrane in at least three ways including serum-dependent binding to CD14 and to a lectin-like receptor, and serum-independent hydrophobic interactions.

Antigens, CD↗
PubMed1991

[Induction of interleukin-1 synthesis. A new criterion of biocompatibility of extracorporeal circuits].

The interaction of plasma with artificial surfaces may result in activation of the complement system with release of the anaphylatoxins C3a and C5a. Some of the biological effects of the anaphylatoxins do not occur immediately since they require de novo protein synthesis, such as the production of the proinflammatory cytokines IL-1, IL-6 and TNF alpha by activated monocytes. We have demonstrated that complement activation is associated with the acute ad transient induction of IL-1 production in patients undergoing hemodialysis with complement activating cellulosic membranes. In patients dialyzed with non-complement activating membranes, a chronic induction of IL-1 production is observed, which may be due to transmembrane passage into the blood compartment of endotoxins contaminating the dialysate. Induction of IL-1 production also occurs in patients undergoing cardiopulmonary bypass. Induction of monocytic interleukins synthesis may be considered a novel criterion of biocompatibility of artificial surfaces for medical use.

Biocompatible Materials↗
PubMed1991

Establishing the relationship between complement activation and stimulation of phagocyte oxidative metabolism in hemodialyzed patients: a randomized prospective study.

The present prospective study was conducted in order to establish the relationship between complement activation and stimulation of phagocyte oxidative metabolism observed in long-term hemodialysis (HD) patients during the early phase of dialysis with cellulosic membranes. Two groups of 10 randomized (HD) patients treated with cellulosic (Cuprophan, CUP) or synthetic polyacrilonitrile (PAN AN-69) membranes were studied. Leukocyte counts, C3a antigen plasma concentration and whole blood basal and stimulated chemiluminescence (CL) production were determined in blood samples drawn from the fistula before dialysis (T0) and from both the afferent and efferent lines of the dialyser at 15 min (T15) and at the end (Tend) of the dialysis session. This study confirms that, coincident with the nadir of leukopenia observed at T15, dialysis with CUP but not PAN membranes induces a marked rise in C3a antigen levels and profound alterations in whole blood CL production consisting of a dramatic increase in basal CL and a significant loss in CL response capacity to stimulating agents. It further demonstrates that a direct relationship exists between the variations in C3a antigen plasma levels and whole blood CL production observed in the CUP group of patients from T0 to T15 (delta 15) of dialysis. This relationship is characterized by a positive correlation between delta 15 C3a and delta 15 basal CL levels in afferent and efferent lines, and a negative correlation between delta 15 C3a and delta 15 CL response capacity values in the efferent but not afferent line. In contrast, no significant correlation with the type of dialysis membrane could be demonstrated between the variations in polymorphonuclear neutrophil counts and C3a antigen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1991

Bacterial lipopolysaccharides alter human endothelial cell morphology in vitro independent of cytokine secretion.

Lipopolysaccharides derived from six bacterial species were found to alter human endothelial cell morphology in vitro in a species-dependent and dose-dependent manner. Lipopolysaccharides derived from Salmonella enteritidis (SeLPS) induced the strongest response, whereas lipopolysaccharides from Vibrio cholerae produced no effect. Cell-shape changes induced by SeLPS (10 micrograms/ml) were noticeable by 24 hours and reached a maximum by 72 hours, thus paralleling the effects produced by the recombinant cytokines interferon gamma (IFN-gamma) (10(3) U/ml), tumor necrosis factor (10(2) U/ml), and interleukin-1 (5 to 10 U/ml). Pretreatment of human endothelial cells with IFN-gamma (10(3) U/ml) for 24 hours induced an accelerated morphologic response to subsequent SeLPS (10 micrograms/ml) stimulation and vice versa, suggesting independent pathways of action. Simultaneous treatment of human endothelial cells with SeLPS and IFN-gamma produced a more rapid onset of morphologic changes and a stronger overall effect. Culture medium containing polymyxin B inhibited cell-shape changes induced by lipopolysaccharides but not those induced by the cytokines. Conditioned medium generated over a 12-hour period following a 24-hour SeLPS/IFN-gamma stimulation did not contain measurable cytokine antigens, nor did it induce biologic responses associated with interleukin-1, IFN-gamma, and tumor necrosis factor alpha. The results indicate that lipopolysaccharides act directly on endothelial cells as well as synergistically with IFN-gamma to alter cell morphology and may, therefore, contribute to the vascular pathology of gram-negative infections.

Bacterial Toxins↗
PubMed1990

Induction of IL-1 release through stimulation of the C3b/C4b complement receptor type one (CR1, CD35) on human monocytes.

Soluble polymerized human C3b and C3b bound to Sepharose induced the production of cell-associated IL-1 and the extracellular release of IL-1 activity from cultured human adherent monocytes. Cultures were performed in serum-free conditions in the presence of polymyxin B and of the PG synthesis inhibitor indomethacin. Induction of intracellular IL-1 activity was associated with that of IL-1 alpha and IL-1 beta Ag. Biologically active released IL-1 was IL-1 beta. Monomeric C3b induced cell-associated IL-1 but not the release of IL-1 from monocytes. IL-1 production was also induced by stimulation of CR1 on adherent monocytes with anti-C3b receptor (CR1) antibody. The ability of multivalent C3b to induce IL-1 production could be dissociated from that of possibly contaminating LPS by several criteria including: the lack of detectable LPS in purified C3b; functional inhibition of LPS in cultures with polymyxin B; the lack of induction of extracellular IL-1 by C3b monomer; a correlation between the expression of CR1 on monocytes and the monocytic response to C3b; a dissociation between the expression of CR1, and the expression of LPS binding sites and the IL-1 response of monocytes to endotoxin. Induction of IL-1 represents a novel pathway by which C3b-CR1 interactions may modulate the immune response.

Cells, Cultured↗
PubMed1990

Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide-stimulated monocytes and macrophages.

Lipopolysaccharide (LPS) is a potent inducer of interleukin 1 (IL 1) synthesis and release, and of tumor necrosis factor (TNF) secretion. Many signals can enhance the LPS-induced production of these cytokines. We have previously observed that addition of low amounts of normal human serum to the culture medium enhances IL 1 production. Among serum factors, anaphylatoxins C3a and C5a and/or their desArg derivatives have been shown to enhance LPS-induced IL 1 and TNF production. However, the capacity of natural anaphylatoxins to induce by themselves the production of cytokines remains a controversial issue. We have investigated the capacity of human recombinant C5a (hrC5a) to induce IL 1 and TNF production. Despite its lack of direct triggering, hrC5a was able to act synergistically with LPS, leading to higher IL 1 and TNF release by human monocytes and mouse peritoneal macrophages. As assessed by the comitogenic assay, hrC5a increased IL 1 release, whereas cell-associated IL 1 activity was not significantly modified. Measurement by enzyme-linked immunosorbent assay of human IL 1 beta led to similar conclusions, whereas measurement of IL 1 alpha by radioimmunoassay indicated, in addition, an increase in intracellular IL 1 alpha.

Animals↗
PubMed1990

Induction of cell-associated interleukin 1 through stimulation of the adhesion-promoting proteins LFA-1 (CD11a/CD18) and CR3 (CD11b/CD18) of human monocytes.

Serum-free culture of human monocytes in the presence of monoclonal antibodies to the LFA-1 alpha chain (CD11a), CR3 alpha chain (CD11b) or beta chain (CD18) bound to Sepharose induced the dose-dependent production of cell-associated interleukin (IL) 1 activity and of IL 1 alpha and IL 1 beta antigens, but no release of extracellular IL 1 activity or antigen in the culture medium. Triggering of IL 1 production was also observed with insolubilized anti-CD11/CD18 F(ab')2 antibodies. Two cross-linked antibodies recognizing distinct epitopes on the CD11b molecule induced cell-associated IL 1. Soluble antibodies did not induce IL 1 production. The kinetics of induction of IL 1 by stimulation of adhesion-promoting proteins differed from those of IL 1 induction by adhesion to plastic. The lack of induction of IL 1 release by stimulation of the CD11/CD18 molecules resembled the intracellular accumulation of IL 1 induced by lipid A. Induction of IL 1 by adhesive processes may be a mechanism by which T cells trigger IL 1 production by monocytes during antigen presentation.

Antigens, Differentiation↗
PubMed1990

Dissociation between the interleukin 1-inducing capacity and Limulus reactivity of lipopolysaccharides from gram-negative bacteria.

In this study we compared the interleukin 1 (IL 1)-inducing capacity and the reactivity in the Limulus amoebocyte assay (LAL) of purified lipopolysaccharides (LPSs) from various bacterial strains. LPSs differed greatly in their capacities (on a weight basis) to induce IL 1 release from serum-free cultured human monocytes. LPS species that induced high levels of IL 1 release from human monocytes exhibited a high thiobarbiturate-reactive 2-keto-3-deoxy-octonic acid (KDO) content. No relationship was found between the IL 1-inducing activity and the LAL reactivity of purified LPSs. Filtration experiments in which membranes of decreasing size-exclusion limits were used demonstrated that molecular species of LPS with an apparent Mr below 3,000 may induce IL 1, whereas only species with an apparent Mr above 8,000 are recognized in the LAL assay. The latter observation suggests that the reaction with LAL requires an aggregated form of LPS. These results indicate that biologically active LPS species can cross dialysis membranes in vivo although no LAL reactive material is detected in the blood compartment. The Limulus assay is an insufficient criterion for the absence of LPS in biological fluids.

Gram-Negative Bacteria↗