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Biomedical subjects

C Capo

Publications and source records attributed to C Capo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of cytotoxic necrotizing factor-1 on actin cytoskeleton in human monocytes: role in the regulation of integrin-dependent phagocytosis.

Cytotoxic necrotizing factor-1 (CNF1) is isolated from pathogenic strains of Escherichia coli and catalyzes the activation of Rho GTPases by the deamidation of a glutamine residue. This toxin induces stress fiber formation, cell spreading, and membrane folding and promotes phagocytosis competence in epithelial cells. We show that CNF1 induces morphologic changes in monocytic cells: polarized-like shape in THP-1 cells, lamellipodia, and cell spreading in adherent monocytes. CNF1 also increased filamentous actin (F-actin) content in a time- and dose-dependent manner. In addition, the toxin profoundly reorganized the actin cytoskeleton: redistribution of F-actin in polarized deformations of THP-1 cells and disorganization of microfilament network in monocytes. We also studied the effects of CNF1 on phagocytosis. It markedly impaired the ingestion of unopsonized zymosan involving CR type 3. However, CNF1 had no effect on the uptake of iC3b-coated zymosan or IgG-mediated phagocytosis of SRBC. In addition, CNF1 induced clustering of CR3 and Fc gammaRII (CD32) but selectively impaired the colocalization of CR3 with F-actin. It is likely that CNF1-induced reorganization of actin cytoskeleton down-modulates integrin activation-dependent phagocytosis by preventing the codistribution of CR3 with F-actin. CNF1 may control some features of integrin-dependent phagocytosis in myeloid cells through its action on Rho GTP binding proteins and cytoskeletal organization.

Actins↗
PubMed1998

IL-10 synthesis and secretion by peripheral blood mononuclear cells in haemodialysis patients.

PURPOSE OF STUDY: IL-10 may explain the paradox between immunodeficiency and oversecretion of cytokines in chronic haemodialysis (HD) patients. We analysed the secretion of IL-10 by PBMC and the expression of IL-10 mRNA in 10 long-term HD patients (108-276 months), 10 short-term HD patients (3-18 months), and 10 healthy controls. RESULTS: Spontaneous IL-10 secretion was higher in HD patients than in controls (15 pg/ml vs 2 pg/ml, P = 0.004). It was detected in 13 of 20 patients and in 1 of 10 controls (P = 0.01). IL-10 mRNA expression was also higher in HD patients than in controls. Spontaneous secretions of IL-10 and IL-6 were positively correlated in patients. IL-10 secretion in response to LPS was higher than the upper limit of control range in 4 of 10 long-term HD patients and in no short-term HD patients (P = 0.04). IL-10 mRNA expression was also higher in long-term than in short-term HD patients. CONCLUSIONS: This study demonstrates that IL-10 is spontaneously synthesized and secreted in HD patients, supporting an immunomodulating role in this setting. The greater IL-10-producing capacity in long-term HD patients indicates a chronic effect of haemodialysis on PBMC responsiveness.

Adult↗
PubMed1998

Increases in the levels of Coxiella burnetii-specific immunoglobulin G1 and G3 antibodies in acute Q fever and chronic Q fever.

A detailed analysis of the humoral response to Coxiella burnetii may provide insight into the pathogenesis of Q fever, a zoonosis caused by C. burnetii. The subclasses of C. burnetii-specific antibodies were determined by immunofluorescence in 20 patients with acute Q fever and 20 patients with chronic Q fever. Although immunoglobulin G1 (IgG1) and IgG3 antibodies were found in acute and chronic Q fever, neither IgG2 nor IgG4 was detected. The detection of IgG1 and IgG3 antibodies was not due to an increase of the IgG1 and IgG3 subclasses. Moreover, IgG1 and IgG3 antibodies were not correlated, suggesting that they may play different roles in Q fever.

Acute Disease↗
PubMed1998

Coxiella burnetii induces reorganization of the actin cytoskeleton in human monocytes.

Coxiella burnetii, an obligate intracellular bacterium which survives in myeloid cells, causes Q fever in humans. We previously demonstrated that virulent C. burnetii organisms are poorly internalized by monocytes compared to avirulent variants. We hypothesized that a differential mobilization of the actin cytoskeleton may account for this distinct phagocytic behavior. Scanning electron microscopy demonstrated that virulent C. burnetii stimulated profound and polymorphic changes in the morphology of THP-1 monocytes, consisting of membrane protrusions and polarized projections. These changes were transient, requiring 5 min to reach their maximum extent and vanishing after 60 min of incubation. In contrast, avirulent variants of C. burnetii did not induce any significant changes in cell morphology. The distribution of filamentous actin (F-actin) was then studied with a specific probe, bodipy phallacidin. Virulent C. burnetii induced a profound and transient reorganization of F-actin, accompanied by an increase in the F-actin content of THP-1 cells. F-actin was colocalized with myosin in cell protrusions, suggesting that actin polymerization and the tension of actin-myosin filaments play a role in C. burnetii-induced morphological changes. In addition, contact between the cell and the bacterium seems to be necessary to induce cytoskeleton reorganization. Bacterial supernatants did not stimulate actin remodeling, and virulent C. burnetii organisms were found in close apposition with F-actin protrusions. The manipulation of the actin cytoskeleton by C. burnetii may therefore play a critical role in the internalization strategy of this bacterium.

Actins↗
PubMed1997

Effect of Val 73 --> Trp mutation on the reaction of "cambialistic" superoxide dismutase from Propionibacterium shermanii with hydrogen peroxide.

The H2O2 inactivation of the "cambialistic" superoxide dismutases from Propionibacterium shermanii, which is active with either iron or manganese at the active site, has been studied in the native and Val 73 --> Trp mutant enzymes. The wild-type iron-containing form of this enzyme is much more resistant to treatment with H2O2 with respect to the other metal-specific Fe superoxide dismutase isoenzymes. After incubation with high amounts of H2O2 the enzyme maintains more than 40% of the initial activity. The activity of the Val 73 --> Trp mutant drastically decreases to less than 5% of the initial activity after incubation with hydrogen peroxide. Amino acid analysis of the H2O2-treated mutant enzyme evidenced the loss of the Trp 73 residue which is shown to play a critical role in the stabilization of the monomer fold of the enzyme. On the other hand, the manganese-containing wild-type and mutant enzymes were completely resistant toward H2O2 demonstrating the specific role of iron in the inactivation process.

Binding Sites↗
PubMed1997

A differential role for interleukin-6 and tumor necrosis factor-alpha in schizophrenia?

Pro-inflammatory cytokines are dysregulated in schizophrenia. To determine the nature of the so-called inflammatory syndrome in schizophrenia, we investigated the circulating levels of various cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)alpha), their natural antagonist (IL1-ra, TNF-RI, TNF-RII) and leukocyte activation markers (the soluble receptor of interleukin-2, soluble CD14 and soluble CD23) in subjects with chronic schizophrenia (n = 18) and in normal controls (n = 21). The levels of IL-1 beta and its antagonist and the levels of leukocyte activation markers were not significantly differents between patients and controls. Circulating levels of TNF alpha were significantly (p < 0.05) higher in patients than in controls and did not result from variations of its antagonist levels. The significant (p < 0.05) increase in patient IL-6 was related specifically to clinical status, i.e. illness duration. These data suggest a specific cytokine-mediated syndrome in schizophrenia. We hypothesize that TNF alpha and IL-6 reflect the genetic background of disease suceptibility.

Adolescent↗
PubMed1997

Characterization of Cu,Zn superoxide dismutase from the bathophile fish, Lampanyctus crocodilus.

Cu,Zn SOD from the bathophile teleost Lampanyctus crocodilus (LSOD) shows a high degree of homology with the sequence of the enzymes from other teleostean fish species. The catalytic properties of LSOD are very similar to those of the bovine enzyme, albeit with higher sensitivity to thermal denaturation. The apparent molecular mass of LSOD (37.6 KDa) is higher than the other Cu,Zn SOD variants studied. The aminoacid sequence of LSOD reveals interesting substitutions compared to the bovine enzyme. These are discussed in view of the particular environmental conditions to which L. crocodilus is adapted.

Amino Acid Sequence↗
PubMed1997

A biological role for haemagglutination activity of Leishmania promastigotes and amastigotes.

Leishmania promastigotes and axenic amastigotes possess a haemagglutination activity (HA). Leishmania attachment to human macrophages was studied after a 30 min incubation in the presence of 10 mM carbohydrates at 37 degrees C. Galactosamine, sialic acid, heparin, mannose, and NAc-mannosamine impaired the attachment of promastigotes and amastigotes to monocyte-derived macrophages and the myelomonocytic cell line THP 1 whereas other carbohydrates had no effect. Preincubation experiments showed that mannose inhibits the macrophage receptor, whereas galactosamine acts on promastigotes. Moreover, the HA is considerably decreased after incubation with macrophages. Our results suggest that promastigotes of different Leishmania species and axenic amastigotes possess a lectin-like receptor with similar specificity, which is in some way involved in the attachment to vertebrate host cells.

Animals↗
PubMed1997

Coxiella burnetii: the 'query' fever bacterium. A model of immune subversion by a strictly intracellular microorganism.

Although substantial progress occurred in the knowledge of Coxiella burnetii during the past years, the pathophysiology of Q fever is still obscure. Emerging evidence from clinical investigations suggested that certain disorders of cell-mediated immunity play a pivotal role in Q fever and especially in its chronic form. This review analyses the potential strategies that C. burnetii, a strictly intracellular pathogen, use to divert microbicidal mechanisms of macrophages and to depress protective T-cell mediated immunity. The role of monocytes in the induction of Q fever is specifically discussed.

Humans↗
PubMed1996

The Cu,Zn superoxide dismutase from Escherichia coli retains monomeric structure at high protein concentration. Evidence for altered subunit interaction in all the bacteriocupreins.

Gel-filtration chromatography experiments performed at high protein concentrations demonstrate that the Cu,Zn superoxide dismutase from Escherichia coli is monomeric irrespective of the buffer and of ionic strength. The catalytic activity of the recombinant enzyme is comparable with that of eukaryotic isoenzymes, indicating that the dimeric structure commonly found in Cu,Zn superoxide dismutases is not necessary to ensure efficient catalysis. The analysis of the amino acid sequences suggests that an altered interaction between subunits occurs in all bacterial Cu,Zn superoxide dismutases. The substitution of hydrophobic residues with charged ones at positions located at the dimer interface of all known Cu,Zn superoxide dismutases could be specifically responsible for the monomeric structure of the E. coli enzyme.

Amino Acid Sequence↗
PubMed1996

Trypanosoma cruzi-induced tyrosine phosphorylation in murine peritoneal macrophages.

Trypanosoma cruzi, the etiological agent of Chagas' disease, binds to and invades macrophages and other cells (fibroblasts, muscle cells) via a complicated set of interactions, but the changes induced by parasite-to-cell interactions are largely unknown. This report investigates the ability of T. cruzi to elicit a tyrosine kinase pathway in immature and mature resident murine peritoneal macrophages (MPM) that differ in their susceptibility to parasite infection. T. cruzi stimulated the phosphorylation of tyrosine residues in several endogenous substrates (proteins of 40-42, 53-56, 66, 75, 80, 90, 95, 100, and 112 kDa), but only in immature MPM. Mature MPM had high levels of spontaneous tyrosine phosphorylation. Upstream tyrosine kinases, such as src-like tyrosine kinases, were not responsible for the differential patterns of tyrosine phosphorylation since they were present in both mature and immature MPM. We suggest that the tyrosine phosphorylation patterns stimulated by T. cruzi reflect most of the biochemical events that occur in parasite host-cell interactions.

Animals↗
PubMed1996

Monocyte production of transforming growth factor beta in long-term hemodialysis: modulation by hemodialysis membranes.

Cytokines are likely involved in hemodialysis-associated complications such as immunodeficiency and beta 2 microglobulin amyloidosis. Because transforming growth factors beta (TGF beta) exert immunosuppressive effects on lymphocytes, down-modulate monocyte functions, and promote fibrosis, we hypothesize that they participate in the deleterious effects of hemodialysis. We investigated the production of TGF beta 1 and TGF beta 2 by monocytes from controls and patients dialyzed with high-flux cellulose triacetate (CT) and polyacrylonitrile (PAN) membranes. The detection of both TGF beta s required an acidification step, suggesting that they are secreted as latent complexes. The spontaneous production of TGF beta 1 and TGF beta 2 was significantly higher in patients dialyzed with CT or PAN than in controls, but the oversecretion of TGF beta 1 was more sustained in CT-treated patients than in PAN-dialyzed patients. The production of interleukin-6 (IL-6) was increased in both patient groups as compared with controls. In contrast to TGF beta 1, the increase was greater in PAN-treated patients than in CT-treated patients, and the release of tumor necrosis factor alpha (TNF alpha) was increased only in PAN-treated patients. Taken together, our results show that hemodialysis is associated with the oversecretion of monocyte cytokines. Moreover, the type of dialysis membrane specifically affects the balance between the secretion of suppressive cytokines such as TGF beta and that of inflammatory cytokines such as IL-6 and TNF alpha.

Acrylic Resins↗
PubMed1996

Production of interleukin-10 and transforming growth factor beta by peripheral blood mononuclear cells in Q fever endocarditis.

The pathophysiology of Q fever endocarditis is characterized by the suppression of antigen-specific cell-mediated immune responses. We investigated the production of interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), known to interfere with the development of protective cell immunity. IL-10 was markedly released by unstimulated peripheral blood mononuclear cells (PBMC) from patients with Q fever endocarditis. This release resulted from the upregulation of IL-10 gene transcription. Similarly, the release of TGF-beta1 and TGF-beta2 was significantly higher in patient PBMC than in control cells, but the expression of their respective mRNA was not enhanced in patient cells. In contrast, lipopolysaccharide-stimulated transcription and release of IL-10 and TGF-beta were similar in patients and controls. The release of IL-10 by PBMC but not that of TGF-beta was correlated with the clinical status of the patients. First, IL-10 production was correlated with specific antibody levels. Second, IL-10 release remained elevated in patients prone to relapse. Taken together, our results suggest that the release of IL-10 and TGF-beta is upregulated in Q fever endocarditis. IL-10 might be considered as a marker of disease relapses and might be instrumental in monitoring the efficiency of the treatment.

Adult↗
PubMed1996

Upregulation of tumor necrosis factor alpha and interleukin-1 beta in Q fever endocarditis.

The occurrence of Q fever endocarditis likely involves some alterations in the responses of monocytes, the in vivo targets of Coxiella burnetii. To test this hypothesis, the production of the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 was assessed in monocytes from patients with Q fever endocarditis. Spontaneous transcription and secretion of tumor necrosis factor and interleukin-1 were significantly higher in patient monocytes than in healthy controls. The interleukin-6 transcripts were also upregulated in patient cells. Moreover, in patients with recent endocarditis exhibiting high titers of immunoglobulin G directed to C. burnetii in phase I, monocytes released significantly higher levels of tumor necrosis factor and interleukin-1 than in patients with stabilized endocarditis. Immunoglobulin G titers and the overproduction of tumor necrosis factor and interleukin-1 were significantly correlated. Hence, the overproduction of inflammatory cytokines might be a marker of disease activity.

Adult↗
PubMed1996

Balance between alveolar macrophage IL-6 and TGF-beta in lung-transplant recipients. Marseille and Montréal Lung Transplantation Group.

Acute inflammation in the lung is characterized by a phase of tissue injury followed by a phase of tissue repair. When the latter is excessive, fibrosis occurs. Alveolar macrophages (AM) can produce cytokines involved in both phases of acute lung inflammation, notably interleukin-6 (IL-6), involved in injury and transforming growth factor-beta (TGF-beta), mediating repair. We hypothesized that AM were activated in both phases, and studied IL-6 and TGF-beta production by AM during complications of lung transplantation, acute rejection (AR), and cytomegalovirus pneumonitis (CMVP). In addition, we analyzed these cytokines in bronchiolitis obliterans (BO), a fibrotic complication of lung transplantation linked to previous AR and CMVP. At the onset of AR and CMVP, IL-6 secretion increased, whereas AM TGF-beta content was increased, but not its secretion. In contrast, with time, IL-6 reached control value whereas TGF-beta secretion rose significantly. In BO, IL-6 was not oversecreted, but TGF-beta increased, notably before functional abnormalities occurred. These results show that during acute complications of lung transplantation, AM display an early activation with oversecretion of IL-6, which is involved in tissue injury, counterbalanced by a late activation in which TGF-beta predominates, mediating tissue repair. The results provide new insights into the pathogenesis of BO, which is linked to acute complications of lung transplantation through this biphasic AM activation.

Adolescent↗
PubMed1996

Latex allergy: allergen identification in Hevea braziliensis fractions by immunoblotting.

BACKGROUND: Latex is the cause of several clinical symptoms of allergy, but the identification of allergens is not completely known. OBJECTIVE: The aim of this report was to study the immunoreactivity of purified stable latex fractions from Hevea braziliensis. METHODS: We purified the cytoplasm of Hevea braziliensis and obtained three fractions: latex particles (LP), lutoids (L) and cytosolic serum (CS). Using Western blot, specific IgE directed to latex allergens was found in 80 patients with latex allergy. RESULTS: Five major groups of allergens migrating as 14, 25, 29, 37-45 and 50 kDa were recognized. They were unequally distributed with the latex fractions: 37-45 kDa proteins were essentially recognized in CS and LP, whereas 14 and 29 kDa proteins were mainly labelled in the L fraction. As a control, aqueous glove extracts exhibited a more restricted pattern of reactivity, because only 14 and 29 kDa proteins were recognized by patient sera. The pattern of reactivity was not correlated specifically with IgE levels, but sera from patients suffering from spina bifida reacted specifically with the minor protein of 25 kDa located in LP. CONCLUSIONS: The present results show that latex allergic patients recognize several allergens which are differently distributed in subcellular fractions extracted from H. braziliensis and aqueous GE. The L fraction and GE were enriched in low molecular weight proteins and apparently contained the same allergens.

Adolescent↗
PubMed1995

Zymosan-triggered association of tyrosine phosphoproteins and lyn kinase with cytoskeleton in human monocytes.

Phagocytosis of pathogens and inert particles such as zymosan by macrophages, and related secretory functions require the combination of several intracellular signals and the reorganization of cytoskeleton. We recently reported that zymosan stimulated the tyrosine phosphorylations of several endogenous substrates in human monocytes. In this work, the relationship between zymosan-stimulated tyrosine phosphoproteins and detergent-insoluble material considered as cytoskeleton was investigated. Triton X-100-insoluble fraction contained two proteins of 53 and 56 kDa that were tyrosine phosphorylated after only 5 min of stimulation with zymosan and remained labeled for 30 min. Because 53- and 56-kDa phosphoproteins migrated, as did some components of the src tyrosine kinase family, namely p53-56lyn, we wondered if 53- and 56-kDa phosphoproteins were related to lyn kinase. First, the amount of immunoreactive p53-56lyn increased in Triton X-100-insoluble fraction as did zymosan-stimulated tyrosine phosphoproteins. This property of p53-56lyn was unique, as no other member of the src family was found in this fraction. Second, when the immunoblots were reprobed with anti-phosphotyrosine mAb, the m.w. of p53-56lyn and tyrosine-phosphorylated proteins were identical in apparent size. Third, p53-56lyn was probably activated after cell stimulation with zymosan, because the phosphorylation levels of a synthetic copolymer of glutamine-tyrosine were increased in Triton X-100-insoluble fraction. In addition, we studied the distribution of lyn kinase and tyrosine phosphoproteins in phagocytozing monocytes. By using immunofluorescence, we showed that lyn kinase was located preferentially in the periphagosomal region in a specific manner, as an src tyrosine kinase such as p59hck, which was not associated with cytoskeleton, was not concentrated around the vacuoles. Moreover, periphagosomal phosphoproteins were also detected and found to be colocalized with polymerized actin. Because zymosan interacts with human monocytes via beta 2 integrins, which are known to be cytoskeleton-associated, we suggest that p53-56lyn provides the molecular link between zymosan receptors and cytoskeleton, and directs the cytoskeletal reorganization in the periphagosomal area.

Blotting, Western↗