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Biomedical subjects

N Haeffner-Cavaillon

Publications and source records attributed to N Haeffner-Cavaillon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Flow-cytometric assessment of in vivo cytokine-producing monocytes in HIV-infected patients.

We have used two-color flow cytometry to study in vivo monocytic cytokine production at the single-cell level in HIV-infected patients. We demonstrated the presence of intracellular IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha in circulating CD14+ monocytes from HIV-infected patients. The specificity of intracellular staining with anti-cytokine antibodies was demonstrated by the suppression of the fluorescent signal when staining was performed in the presence of recombinant cytokines. We did not detect any specific intracellular staining when anti-IL-4 antibodies were used since monocytes do not produce IL-4. In vivo intracellular cytokine production of IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha was higher in monocytes from HIV-infected individuals compared to monocytes from healthy controls; however, only the data concerning IL-1 alpha reached statistical significance. Monocytic cytokines are involved in the regulation of HIV gene expression and may participate in the modulation of the Th1/Th2 balance. The ability to follow the production of a wide range of cytokines by circulating monocytes of HIV-infected patients should allow one to better analyze the role of monocytic cytokines in the pathogenesis of HIV disease.

Cytokines↗
PubMed1997

Normal human immunoglobulins for intravenous use (IVIg) delay hyperacute xenograft rejection through F(ab')2-mediated anti-complement activity.

Xenotransplantation between discordant species leads to a hyperacute rejection mediated by natural antibodies, both of the IgG and IgM isotypes, activation of complement and endothelial cell activation. The combination of these mechanisms leads to a transplant survival of minutes to a few hours. Polyclonal human immunoglobulins for intravenous use (IVIg) from normal donors have proved effective in a number of antibody-mediated disorders, as well as in inflammatory disorders. We demonstrate that administration of IVIg in a guinea pig to rat model of cardiac xenografting can effectively delay hyperacute rejection. This effect is mediated by the F(ab')2 fragments of IVIg, and is correlated to an anti-complementary activity.

Acute Disease↗
PubMed1997

Plasma levels of monocyte chemoattractant protein-1 but not those of macrophage inhibitory protein-1alpha and RANTES correlate with virus load in human immunodeficiency virus infection.

Plasma levels of proinflammatory cytokines, cytokine inhibitors, and the beta chemokines RANTES, macrophage inhibitory protein (MIP)-1alpha, and monocyte chemoattractant protein (MCP)-1 were studied in relationship with virus load in 40 patients exhibiting plasma levels of HIV RNA ranging between undetectable and levels >10(6) copies/mL. Mean plasma levels of MCP-1 were increased in patients with high virus load compared with HIV-seropositive subjects with undetectable plasma viral RNA and healthy controls. MCP-1 levels were directly correlated with plasma levels of HIV RNA. No correlation was observed between virus load and plasma concentrations of MIP-1alpha and RANTES. The results suggest that low rates of viral replication in vivo are not dependent on increased production of the suppressive chemokines RANTES and MIP-1alpha. Since MCP-1 upregulates viral replication in vitro, the results may suggest a role for MCP-1 in triggering viral replication in HIV disease.

Chemokine CCL2↗
PubMed1997

Dissociation between beta-2 microglobulin and IL-1 production in hemodialyzed patients.

BACKGROUND: beta-2 microglobulin is predominant in amyloid deposits in patients undergoing long term hemodialysis. Amyloid accumulation has been ascribed to dialysis membranes, endotoxin contamination of the dialysate, uremia and chronic systemic inflammation associated with enhanced monocytic cytokine production in hemodialyzed patients. Interleukin-1 has been proposed to play a critical role in the induction of beta-2 microglobulin synthesis and release. METHODS: We examined if monocytes contribute to beta-2 microglobulin production upon stimulation with inflammatory mediators that are generated during hemodialysis and investigated the production of beta-2 microglobulin by cells from patients, with and without clinical signs of amyloidosis, at the time when patients' monocytes contained maximal intracellular accumulation of IL-1. RESULTS: We demonstrated that only monocytes are able to release increased levels of beta-2 microglobulin upon stimulation by IL-1, TNF alpha, C5a and LPS. Increased levels of beta-2 microglobulin were associated with increased levels of beta-2 microglobulin mRNA. Before dialysis session, 20-60% of circulating CD14+ monocytes from patients contained IL-1. At the time when maximal IL-1 production was detected, we showed by RT-PCR increased transcription of IL-1 gene in patients' monocytes. We observed that monocytes from patients with amyloidosis contained higher amounts of IL-1 as compared to monocytes from patients without clinical signs of amyloidosis, but could not secrete increased amounts of beta-2 microglobulin upon LPS-stimulation. CONCLUSIONS: Our data indicated that chronic inflammation, as demonstrated by increased intracellular IL-1 expression, is not associated with increased production of beta-2 microglobulin by monocytes from patients on hemodialysis.

Adolescent↗
PubMed1997

Neutrophil reactive oxygen species production during hemodialysis: role of activated platelet adhesion to neutrophils through P-selectin.

Platelet interaction with leukocytes can occur to a significant degree during hemodialysis, but it remains to be determined what pathophysiological consequences stem from the intradialytic formation of platelet-leukocyte coaggregates. By the use of flow cytometry techniques, this study was set out to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil hydrogen peroxide production from 10 end-stage renal disease patients each dialyzed with cuprophane and polyacrylonitrile membranes. Platelet-neutrophil coaggregates increased during dialysis with cuprophane, whereas no changes occurred with polyacrylonitrile membranes. Dialysis with cuprophane, unlike that with polyacrylonitrile, also resulted in a significant increase in neutrophil hydrogen peroxide production 10 min after dialysis initiation which persisted at significantly higher levels than predialysis values through the first 20 min. We found that the increased hydrogen peroxide production by neutrophils essentially occurred in concomitance with neutrophil-platelet coaggregation. Intracellular fluorescence representing hydrogen peroxide formation significantly increased through the first 20 min of cuprophane dialysis in neutrophils aggregated to platelets. By contrast, no change occurred in neutrophils not aggregated to platelets. Neutrophils which had formed aggregates with platelets produced higher hydrogen peroxide levels, as assessed by significantly higher fluorescence values, than non-aggregate-forming neutrophils at all time points tested. The phenomenon was duplicated in vitro when ADP-activated normal platelets were incubated with neutrophil cells but was largely inhibited when ADP-activated platelets were treated with anti-P-selectin antibody before incubation with neutrophils. These results strongly suggest that platelet-neutrophil aggregates occurring during hemodialysis, representing cell-cell interactions with pathophysiological effects, may serve as a new parameter to assess biocompatibility.

Adenosine Diphosphate↗
PubMed1997

Effects of non-steroidal antiallergic eyedrops on the complement-mediated histamine release from human cells.

Leukocytes from ten allergic patients (five allergic to dust-mites and five allergic to pollen) were treated with N-acetyl aspartyl glutamic acid (NAAGA) 4.9%, disodium cromoglycate (DSCG) 2%, lodoxamide (LODO) 1%, and levocabastine (LEVO) 0.5% (concentrations representing the pharmaceutical eyedrop preparations) for 20 minutes. Degranulation was then induced with Complement (rHu5Ca). Histamine was measured in the supernatant with ELISA. LODO and LEVO were inactive in blocking histamine released from human cells, and paradoxical unexpected effects were found with these two agents. They both induced significant histamine release in almost 100% of the samples. DSCG was able to block histamine release in seven patients out of nine (ranging between 5 and 34%). NAAGA was the most active agent on human cells and was able to block basophil degranulation in nine patients out of nine (inhibition ranging between 4 and 66% of total histamine pool).

Allergens↗
PubMed1996

Cell-associated adhesion molecules as early markers of bioincompatibility.

BACKGROUND: Transient nature of adhesive interactions occurring during cell margination is mainly dependent on expression of selectins which are shed by activated cells. This shedding in the circulation may play an important role as anti-inflammatory mediator. Haemodialysis is also associated with P-selectin (CD62P)/sialyl-Lewis(x) (CD15s) interactions which mediate platelet-leukocyte coaggregation. We further investigated the mechanisms underlying leukocyte margination during haemodialysis. METHODS: CD15s, CD11b and CD61 expression on circulating leukocytes from patients dialysed on synthetic membranes (modified polyacrylonitrile (SPAN), polysulphone (PS), and polyacrylonitrile (AN69) was assessed by cytofluorometry in a prospective crossover trial. We measured plasma levels C3a/C3a desArg, soluble CD62P, and CD62E molecules obtained from patients and healthy individuals. RESULTS: Expression of CD11b and CD15s was upregulated on neutrophils from patients dialysed with SPAN and PS membranes during the dialysis session. A significant negative correlation was found between the expression of CD11b or CD15s molecules and neutrophil counts as well as between CD15s expression and monocyte counts during haemodialysis. As assessed by CD61 expression on leukocytes, we observed that platelets bound significantly onto both neutrophils and monocytes during dialysis with both membranes. A significant positive correlation was found between the expression of CD11b molecules and the percentage of CD61+ monocytes counts during SPAN and PS dialysis. We found a significant increase of soluble CD62P in plasma samples obtained from haemodialysed patients before the dialysis session as compared to the levels detected in plasma from healthy individuals. CONCLUSIONS: This study documents a major role of CD15s, CD11b, CD61, CD62P molecules in the transient leukocytes activation and margination during haemodialysis on synthetic membranes despite their low complement-activating properties.

Adult↗
PubMed1995

Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells.

Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time. Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro. The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat. The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells. Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS. We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors. The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors. Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex.

Biological Transport↗
PubMed1995

Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass.

BACKGROUND: The adhesion of neutrophils to endothelial cells and their subsequent transendothelial migration play a major role in inflammatory damage elicited by cardiopulmonary bypass (CPB) because these events are linked to the release of cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking in relation to systemic temperature during clinical CPB have not yet been characterized. METHODS AND RESULTS: Twenty case-matched patients undergoing warm (31.8 +/- 0.4 degrees C) or cold (26.3 +/- 0.5 degrees C, P < .0001 versus warm) bypass were studied. Blood samples were simultaneously collected from the right and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of C3a, P- and E-selectins, elastase, and interleukin-8 were determined by immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement activation, (2) a fall in soluble E-selectin consistent with an increased adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase, suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise in interleukin-8 that is likely to promote transendothelial migration of adherent neutrophils. All of these changes occurred in the two groups of patients and were significant compared with prebypass values. However, in none of the groups was there a significant difference between right and left atrial values for any of the markers. The single difference between cold and warm bypass patients was a significant reduction of elastase release in the cold group (P < .001 versus the warm group). CONCLUSIONS: Clinical CPB is associated with biological changes suggesting the occurrence of neutrophil trafficking. Hypothermia provides only partial protection through a reduced release of elastase. Overall, these results reinforce the rationale for the development of therapeutic strategies targeted at blunting the neutrophil-mediated component of bypass-induced inflammatory damage.

Body Temperature↗
PubMed1995

Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin).

We have investigated the effects of intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL-1ra) and IL-8 in cultures of normal human monocytes. The addition of IVIg to cultures of purified monocytes induced a dose-dependent secretion of IL-1ra and IL-8 without stimulating the production of IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha or IL-6. The effects of IVIg required both the Fc and F(ab')2 portions of IgG. IVIg-induced production of IL-8 by monocytes was enhanced by lipopolysaccharide (LPS), although LPS inhibited the secretion of IL-1ra, suggesting that IVIg and LPS stimulate distinct intracellular pathways in monocytes. Induction of IL-1ra and IL-8 by IVIg was enhanced in the presence of autologous T lymphocytes. Our observations document the selectivity of the effects of IVIg on the synthesis of cytokines and cytokine antagonists by human monocytes. Induction of IL-1ra and IL-8 by IVIg may contribute to the anti-inflammatory effects of immunoglobulin therapy in patients with autoimmune and systemic inflammatory disorders.

Cell Communication↗
PubMed1995

CD14lowCD16high: a cytokine-producing monocyte subset which expands during human immunodeficiency virus infection.

Infection with the human immunodeficiency virus HIV-1 is associated with the expansion of a CD14lowCD16high monocyte subset in peripheral blood. This subset, which represents a minor subpopulation of monocytes in healthy individuals, increases during HIV infection and, in patients with AIDS, may represent up to 40% of the total circulating monocyte cell population. The CD14lowCD16high circulating monocytes co-express MAX.1, p150,95 and HLA-DR which are typical of tissue macrophage markers. These cells also express higher levels of intracellular interleukin (IL)-1 alpha and tumor necrosis factor (TNF)-alpha than the CD14highCD16low monocyte population from the same patients. The CD14lowCD16high cells also express low levels of CD35, CD11a and CD4 in common with normal monocytes. When cultured in vitro, monocytes from HIV-seropositive individuals differentiated within a few hours into an elongated fibroblastoid shape characteristic of migratory cells. Our results suggest that the expansion of the CD14lowCD16high monocyte subset, which produce high amount sof TNF-alpha and IL-1 alpha, may participate in the immune dysfunction observed during HIV infection.

Cell Division↗
PubMed1995

252Cf-plasma desorption mass spectrometry analysis of lipids A obtained by an elimination reaction under mild conditions.

Lipids A are the hydrophobic domains of bacterial endotoxic lipopolysaccharides. Since they are responsible for most of the biological activities (both pathogenic and beneficial) of endotoxins, the characterization of their structure is crucial to the understanding of their mode of action. However, the inadequacy of existing methods for preparing certain lipids A has prompted us to devise a new, mild procedure which gives intact products. Use was made of the special features of 252Cf-plasma desorption mass spectrometry for forming molecular ions from these species and giving qualitative and quantitative information from the primary mass spectrum.

Bordetella pertussis↗
PubMed1995

A major role for CD62P/CD15s interaction in leukocyte margination during hemodialysis.

We investigated expression of several antigens on neutrophils and monocytes, involved in cell adhesion, from patients hemodialyzed with cellulosic and polyacrylonitrile membranes. Among the antigens tested only the expression of CD15s and CD11b was significantly increased on neutrophils and monocytes in patients dialyzed with cellulosic membranes. No changes occurred with polyacrylonitrile membranes. Leukocyte counts from patients dialyzed with cuprophane membranes decreased at the same time as expression of cellular CD15s increased, resulting in a significant negative correlation at all time points tested. No correlation was found between the drop of monocytes and their expression of CD11b. When CD15s expression increased on neutrophils and monocytes, we observed a concomitant increase of CD62P, a specific selectin of activated platelets. When whole blood cells were incubated with complement activated serum both antigens increased but not when cells were incubated with hrC5a. We also observed that CD61, a platelet phenotypic antigen, was present on leukocytes incubated with complement activated serum. At the time when platelet-leukocyte coaggregates decreased, CD62P expression remained stable on leukocytes, suggesting that both neutrophils and monocytes are able to trap either CD62P shed by activated platelets or soluble CD62P present in normal human serum. The present study documents a major role of P-selectin (CD62P)/sialyl-Lewis x (CD15s) interaction in the transient leukocyte margination during hemodialysis.

Acrylic Resins↗
PubMed1995

Antiretroviral therapy suppresses the constitutive production of interleukin-1 associated with human immunodeficiency virus infection.

Interleukin (IL)-1 is constitutively produced by monocytes of human immunodeficiency virus (HIV)-seropositive persons. The changes in the production of IL-1 by monocytes of 24 HIV-infected patients were investigated during the course of 8 months of antiretroviral therapy. At month 8, the amounts of biologically active IL-1 and IL-1 alpha and -beta proteins produced by freshly obtained monocytes and by monocytes cultured for 24 h in the absence of lipopolysaccharide (LPS) decreased significantly compared with pretreatment values or decreased below the limits of detection in the assays. Antiretroviral therapy also resulted in enhanced secretion of IL-1 receptor antagonist (IL-1Ra) by LPS-stimulated patients' monocytes. The reduction in the constitutive production of IL-1 and the increased ability of stimulated cells to produce IL-1Ra associated with antiretroviral therapy may also be of importance in reducing a major pathway of amplification of viral replication in infected monocytes and lymphocytes.

Adult↗
PubMed1995

[Cell adhesion molecules and the immune system].

Cellular interactions are controlled by complex mechanisms which come into play at the receptors on the cell surface (adhesion molecules: selectins, integrins, superfamily of immunoglobulins), the soluble cell mediators (cytokines) and the components of the tissue matrix (fibronectin, collagen, etc.). Disturbance of one of these systems may induce a pathological condition. The physiological state of the individual therefore depends on the balance of all these components. In the development of inflammation, adhesion molecules play an essential role in the localisation of the inflammatory response. At this level, the vascular endothelium, a governing barrier for the exchanges between blood and the tissues, plays an active part in regulation of the transcapillary permeability, control of proliferation of haematopoietic cells and the phases of the inflammatory response. After they have marginated, the active cells migrate by diapedesis towards the site of inflammation by creation of chemotactic signals as the adhesion between the cells is insufficient to induce their migration. The adherence phenomena depend on a process that is strictly controlled by the cytokines and enable intervention of cell-cell reactions and cell-protein recognition of the extra-cellular matrix. Cytokines play a key role in control of the expression and/or avidity of membrane receptors for ligand(s). An appropriate and rapid response of the circulating cells depends on coordination of the train of events that regulate the functional expression of the adhesion molecules. Use of specific antibodies that prevent cell adherence opens very important therapeutic possibilities because a single blockage of cell adhesion can have an immediate direct impact on development of the inflammatory response.

Animals↗
PubMed1995

Adherence of human monocytes to haemodialysis membranes: LFA 1 (CD11a/CD18) CR1 (CD35) and CR3 (CD11b/CD18) triggering promotes the biosynthesis of platelet-activating factor and adherence.

BACKGROUND: Platelet-activating factor is a mediator of inflammation involved in the blood-membrane interaction. We report that selective stimulation of complement receptors (CR1 and CR3) triggers PAF synthesis and monocyte adherence to complement-activating membranes. METHODS: The synthesis of PAF was studied after stimulation of normal human adherent monocytes with F(ab)2 and Fab fragments of monoclonal antibodies specific to CR1 and CR3. CD11a, CD11b, CD18, and CD35 was studied by flow cytometry on neutrophils and monocytes. The molecular species of PAF from stimulated monocytes were identified by reverse-phase high-performance liquid chromatography coupled with mass spectrometry. RESULTS: Anti-CR1 and anti-CR3 monoclonal antibodies induced a dose-dependent C-16 but not C-18 PAF production. The latter occurred also with monovalent Fab fragments of both anti-CR1 and anti-CR3 monoclonal antibodies, that were not internalized as seen by immunofluorescence. Adherence of monocytes to Cuprophan membranes was markedly higher (P < 0.01) in membranes pretreated with fresh than with heat-inactivated normal plasma. However, the high adherence to fresh plasma-treated membranes was completely abrogated by coincubating the cells with Web 2170, a specific PAF receptor antagonist. This was not due to downregulation of adhesion molecules expression on leukocytes. CONCLUSIONS: These studies implicate a crucial role of PAF in blood interaction with haemodialysis membranes that fix complement activated products.

Antibodies, Monoclonal↗
PubMed1995

[Does temperature in extracorporeal circulation affect neutrophil-endothelium interactions?].

The increasing interest in "warm" aerobic cardioplegia requires a critical reevaluation of the systemic effects of the associated normothermic cardiopulmonary bypass (CPB). As activated neutrophils seem to be essential mediators of the inflammatory response to CPB via the cytotoxicity of the products that are released during their adhesion to endothelial cells, the authors undertook a study of the influence of temperature on the interaction between the neutrophils and the endothelium in 95 patients undergoing warm (31-33.5 degrees C, n = 49) and cold (26-27 degrees C, n = 46) CPB surgery. Blood sampling was performed before, during and after CPB. The following markers of neutrophil-endocardium interaction were analysed: complement activation (C3a), cytokine production (tumor necrosis factor alpha, interleukines 1, 6 and 8, and interleukin-1 receptor antagonist); endothelial expression of cytokine-dependent [intercellular adhesion molecule (ICAM)] and cytokine-independent (P-selectin) adhesion molecules (P-selectin); expression of cytokine molecules on the surface of polynuclear neutrophils (CD11a, CD11b, CD11c); and finally, endothelial adhesion and transendothelial migration of neutrophils (interleukin 8 and elastase). The results showed that, irrespective of temperature, CPB was associated with changes strongly suggestive of phenomena of transendothelial adhesion and migration. Moreover, normothermia increased the intensity of the inflammatory response as shown by increased cytokine production, earlier expression of neutrophil adhesion molecules and increased elastase production.

Aged↗