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M T Labro

Publications and source records attributed to M T Labro.

At least 55 records · Page 3Linked to original sources
PubMed1989

Comparison of the in-vitro effect of several macrolides on the oxidative burst of human neutrophils.

We have compared the in-vitro interaction of five macrolides (roxithromycin, erythromycin, spiramycin, oleandomycin and josamycin) with human neutrophils (PMN). Only roxithromycin strongly impaired the oxidative burst of PMN assessed by luminol amplified chemiluminescence, superoxide anion generation, and myeloperoxidase-mediated iodination of proteins. This effect was observed only for high concentrations of this drug (100 and 50 mg/l). Furthermore, the sensitivity of PMN to the depressive effect of roxithromycin permitted the definition of two kinds of PMN: in Highly Sensitive (HS)-PMN, the oxidative response was completely abolished while in Moderately Sensitive (MS)-PMN, a decreased, but yet measurable (20-50% of the control), response was obtained. The roxithromycin-induced depression of PMN was time-dependent and partly reversed by washing. Chemotaxis was also impaired by roxithromycin (100 mg/l) but phagocytosis of Klebsiella pneumoniae was unaltered even at high concentrations of the drug. Since roxithromycin displays the highest intracellular uptake, compared with the other macrolides assessed in this study, this could explain the results observed here. The relevance to the clinical situation needs further study. This effect of roxithromycin could be useful to control the inflammatory process associated in certain infectious diseases, in particular if high concentrations of the drug are obtained in tissues.

Anti-Bacterial Agents↗
PubMed1989

Synergistic interaction of josamycin with human neutrophils bactericidal function in vitro.

Josamycin, a 16-membered ring macrolide is concentrated up to 20-fold in phagocytic cells compared with serum. We have studied the in-vitro interaction of this drug with human neutrophils (PMN) bactericidal function by using two strains resistant to this antibiotic, Pseudomonas aeruginosa and Klebsiella pneumoniae, and a sensitive one, Staphylococcus aureus 209P. It was shown that josamycin-pretreated adherent PMN displayed an increased phagocytic activity (about 30 to 40%) for S. aureus or K. pneumoniae, mainly due to the recruitment of an additional phagocytizing subset of PMN. Furthermore, the bacterial killing was enhanced in josamycin-treated PMN in a dose-dependent manner for K. pneumoniae (60-130% increase in the range of concentration 0.1-25 mg/l) and independently of the dose for S. aureus (about 425-460% increase for josamycin 0.1-10 mg/l). P. aeruginosa killing by whole blood was also significantly increased in the presence of 10 and 1 mg/l of josamycin. Other PMN functions were not much altered by josamycin except an enhancement of the formyl-methionyl-leucyl-phenylalanine-induced oxidative response. Chemotaxis was only increased by the presence of a high concentration (100 mg/l) of josamycin. These data suggest that the bactericidal synergy between PMN and josamycin could be related, partly at least, to a direct enhancing effect of josamycin on some PMN functions such as phagocytosis, chemotaxis and FMLP-induced chemiluminescence. On the other hand, alterations of bacteria, either inside the phagolysosome or in the extracellular medium, could lead to an enhanced susceptibility to the phagocytes' microbial mechanisms.

Chemotaxis, Leukocyte↗
PubMed1989

[Bactericidal synergy of josamycin and human polynuclear neutrophils in vitro].

Due to their high intracellular uptake, macrolides may interfere with phagocytes antibacterial system. We have studied the interaction of josamycin with bactericidal activity of human neutrophils (PMNs) or whole blood, in vitro. PMNs preincubated with josamycin (100-0.1 mg/l) display an increased phagocytic ability for K. pneumoniae, independently of the concentrations of josamycin; this effect appears to correlate with the recruitment of an additional population of phagocytizing PMNs without alteration of the mean number of PMN-associated bacteria, whatever the experimental conditions (adherent or non adherent PMNs). PMNs bactericidal function is also enhanced in the presence of josamycin in a dose-dependent manner (mean increase 60 to 370% for josamycin 0.1 to 10 mg/l). Bactericidal activity of whole human blood for P. aeruginosa (a strain resistant to the lytic effect of serum) is increased with a mean survival (CFUt min/CFU 0 min) of 24 and 71% at 60 and 120 min respectively, in the presence of josamycin 10 mg/l, and 42 and 128% in the presence of josamycin 1 mg/l, compared to the survival of the control, 68 and 166%. PMNs functions are not altered by josamycin with the exception of an enhancement of the oxidative burst induced by formylmethionyl-leucyl-phenylalanine, a synthetic compound similar to bacterial derivatives. In conclusion, we have shown a synergic interaction between phagocytes and josamycin for the killing of bacteria resistant to this antibiotic (MiC greater than 128 mg/l). This could be due either to an alteration of some PMN membrane receptors or to alterations of bacteria which render them more sensitive to natural bactericidal mechanisms and/or more able to activate these mechanisms.

Blood Bactericidal Activity↗
PubMed1988

Influence of subinhibitory concentrations of ceftriaxone on opsonization and killing of Pseudomonas aeruginosa by human neutrophils.

Ceftriaxone, a 2-aminothiazolyl cephalosporin does not alter human neutrophil (PMN) bactericidal function. However, low concentrations of ceftriaxone induce some bacterial strains to be more sensitive to PMN killing. We have studied the effect of a subinhibitory concentration of ceftriaxone (10 mg/l) on Pseudomonas aeruginosa (MIC greater than 128 mg/l). After an overnight exposure to this concentration of ceftriaxone, P. aeruginosa elongated into filaments. PMN killing of ceftriaxone-treated bacteria was better than killing of control bacteria. This enhanced killing was correlated with an increased sensitivity to oxygen-dependent bacterial killing. Furthermore, the altered bacteria induced a greater oxidative response of PMN which was independent of their chemiluminescence response after stimulation by control P. aeruginosa. This increased oxidative burst was attributable to both non-opsonodependent stimulation and to increased deposit of opsonins.

Ceftriaxone↗
PubMed1988

Effects of amodiaquine, chloroquine, and mefloquine on human polymorphonuclear neutrophil function in vitro.

This study concerns the in vitro interaction with human polymorphonuclear neutrophils (PMNs) of amodiaquine, chloroquine, and mefloquine, three antimalarial drugs currently in use for the treatment and prophylaxis of malaria. It was found that mefloquine (100 and 50 micrograms/ml) significantly altered PMN viability while the other two drugs did not. Neutrophil chemotaxis was impaired by chloroquine (100 micrograms/ml) and mefloquine (greater than 10 micrograms/ml) but not by amodiaquine. Phagocytosis was decreased by about 50% in the presence of chloroquine (100 micrograms/ml) or mefloquine (10 micrograms/ml). The three antimalarial drugs altered neutrophil oxidative metabolism as assessed by luminol-amplified chemiluminescence. The strongest effect was observed with mefloquine, which abolished almost completely the neutrophil burst at concentrations of greater than 10 micrograms/ml whatever the stimulus used. This effect was not reversed by washing. Chloroquine and amodiaquine also impaired this PMN response by approximately 80 and 50%, respectively, but only at the highest concentration used (100 micrograms/ml). In the case of amodiaquine, the neutrophil response was restored by washing, except for stimulation with opsonized particles. After washing, the depressive effect of chloroquine was reversed completely in the case of phorbol myristate acetate stimulation and partly in the case of opsonized particle stimulation, but the formylmethionyl-leucyl-phenylalanine-induced response was not restored. These data show that although they are structurally related, amodiaquine and chloroquine exhibit qualitatively and quantitatively different depressive effects on PMN function and probably interfere at different points of cell activation, although the precise mechanisms are as yet unresolved.

Amodiaquine↗
PubMed1988

[Interaction of roxithromycin with human polymorphonuclear neutrophils in vitro and ex vivo].

Roxithromycin (RU 28965) a new semisynthetic macrolide has been reported to display an antibacterial spectrum and activity in vitro similar to those of others macrolides. However, roxithromycin seems more efficient than erythromycin in in vivo experimental infections (mice). We have previously reported that roxithromycin increases the ability of human neutrophils (PMN) for bactericidal activity (S. aureus) or phagocytosis (K. pneumoniae) in vitro without altering other PMN functional parameters. In this study, roxithromycin (single dose-300 mg) was given to 6 human volunteers. The neutrophils collected 90 min after ingestion display a significant increased ability to phagocytose and kill S. aureus and K. pneumoniae. Furthermore chemotaxis, oxidative burst and myeloperoxidase activity of the PMN after roxithromycin ingestion were enhanced compared to those of PMN before ingestion. This discrepancy between immunomodulating effect of roxithromycin in vitro and in vivo outlines the complexity of in vivo experimental models and requires further studies in vivo in particular in patients suffering from sepsis.

Adult↗
PubMed1987

Cefodizime (HR 221) potentiation of human neutrophil oxygen-independent bactericidal activity.

The enhanced bactericidal activity of human neutrophils induced by cefotaxime and cefodizime, two methoxy-imino-amino- 2-thiazolyl cephalosporins, is linked to the cell stimulation of oxygen-dependent and oxygen-independent killing systems, respectively. Cefotaxime enhances both the killing and the oxidative response of neutrophils to opsonized particulate stimuli (bacteria for both activities and opsonized zymosan for the oxidative burst). These effects were not observed with non-opsonized particles (bacteria or zymosan) or soluble stimuli. On the contrary, cefodizime enhances killing of opsonized and non-opsonized bacteria by neutrophils regardless of treatment with phenylbutazone which blocks neutrophil oxidative metabolism. Cefodizime does not universally alter the oxidative burst induced by various stimuli, but has been shown to enhance the bactericidal activity of crude extracts of neutrophil granules. The data suggest that cefodizime and non O2-dependent killing systems of neutrophils cooperate in killing bacteria.

Cefotaxime↗
PubMed1987

Interaction of ceftriaxone with human polymorphonuclear neutrophil function.

Ceftriaxone, an amino-2-thiazolyl cephalosporin, has been shown to cooperate in vitro with human neutrophils for the killing of some bacteria. In this work the direct interaction with human leucocyte bactericidal function has been studied. Ceftriaxone (1000 to 1 mg/l) did not alter neutrophil chemotaxis or superoxide anion production. It also did not interfere with the chemiluminescence response of isolated PMN although a paradoxical depressive effect was observed with whole human blood in the case of zymosan stimulation. The killing of Staphylococcus aureus and Klebsiella pneumoniae was not enhanced by ceftriaxone and phagocytosis was significantly depressed only with adherent neutrophils but not when using neutrophils in liquid medium. It is concluded that the synergy observed between leucocyte and ceftriaxone for bacterial killing cannot be related to a direct stimulation of neutrophil functions and should depend on bacterial alteration.

Blood Bactericidal Activity↗
PubMed1987

Effect of ceftriaxone-induced alterations of bacteria on neutrophil bactericidal function.

Two bacterial strains (Staphylococcus aureus and Klebsiella pneumoniae) were exposed to subinhibitory concentrations of ceftriaxone. After an overnight culture in presence of 1 MIC of ceftriaxone either in broth or on solid medium S. aureus showed enlarged forms which were better phagocytosed (increase about 40%) and killed (increase about 50%) than control staphylococci. Exposure of K. pneumoniae to 0.1 MIC ceftriaxone resulted in filamentation of bacteria. When grown in the presence of 0.01 MIC, K. pneumoniae did not elongate into filaments but were significantly more phagocytosed (increase about 40%) or killed (increase about 170%) than control bacilli. The mechanism of the greater sensitivity to PMN killing of the altered S. aureus and K. pneumoniae was assessed either with phenylbutazone-treated PMN or by in-vitro exposure to crude granule extracts of PMN. The altered bacteria displayed a significant susceptibility to the non-oxidative killing mechanism while untreated bacteria were unaffected by the non-oxidative system. These data could explain the synergy observed between ceftriaxone and leucocytes in the killing of some micro-organisms.

Blood Bactericidal Activity↗
PubMed1987

Inhibitory effect of K-562 malignant cells on locomotion of human neutrophils.

Certain tumor cells generate factors that inhibit neutrophil chemotaxis. The present study was designed to explore, in K-562 malignant cells, the release of such factors that may alter the neutrophil locomotion. The supernatant, separated from the K-562 malignant cells cultured in vitro for 48 hours, was lyophilised and extracted with ethanol 80%. This ethanol extract (SE-K562) inhibited neutrophil locomotion. Both random and locomotion induced either by formyl-methionyl-leucyl-phenylalanine (FMLP) or serum were inhibited. SE-K562 was partially purified by Sephadex chromatography and the analysis of the eluted active fraction by SDS electrophoresis led one band of about 8 kd. No one inhibitory effect was observed with appropriate controls. In conclusion, K562 malignant cells in culture release a low molecular weight factor (8 kd) that inhibits all forms of PMN locomotion i.e. random locomotion and locomotion induced either by FMLP or serum.

Cell Line↗
PubMed1986

Effects of cefotaxime and cefodizime on human granulocyte functions in vitro.

In vitro, cefotaxime and cefodizime enhanced significantly the bactericidal activity of human neutrophils against Staphylococcus aureus P 209 A, but not phagocytosis. The increase was about 150% for cefotaxime and 400% for cefodizime at concentrations as low as 1 mg/l. Furthermore, by two different techniques (NBT and cytochrome C reduction tests) cefotaxime but not cefodizime significantly enhanced superoxide anion production by zymosan-stimulated neutrophils. Other neutrophil functions (chemotaxis and myeloperoxidase-mediated iodination of proteins) were not significantly altered by either antibiotic, even at concentrations as high as 1000 mg/l.

Blood Bactericidal Activity↗
PubMed1986

Synergy between RU 28965 (roxithromycin) and human neutrophils for bactericidal activity in vitro.

The in vitro effects of RU 28965 (roxithromycin), a new semisynthetic macrolide, on human neutrophil activity were compared with those of erythromycin. RU 28965, at a concentration as low as 0.1 microgram/ml, significantly enhanced the phagocytosis and killing of Staphylococcus aureus by neutrophils. Erythromycin displayed a less stimulating effect in a dose-dependent manner. Phagocytosis of Klebsiella pneumoniae was also increased after incubation of neutrophils with RU 28965, but killing was not altered. Neutrophil chemotaxis, myeloperoxidase activity, and O2 consumption were unchanged in the presence of RU 28965.

Blood Bactericidal Activity↗
PubMed1984

Detection of antilymphocyte antibodies in patients with scleroderma using three different techniques.

The occurrence of antilymphocyte antibodies (AL-Ab) was investigated in the sera of 28 patients with scleroderma. By indirect immunofluorescence, we found these Ab in 53% of the sera. Inhibition of E rosette formation and lymphocytotoxicity revealed these Ab in 42% and 14% of the sera respectively. Most of the Ab (93%) reacted at 0 degrees C. These AL-Ab can be separated into several groups depending on their inhibitory activity on the lymphocyte membrane. In some cases, the receptor seems similar to that of sheep red blood cells. The study of the clinical features of the patients showed few differences between the groups with and those without Al-Ab. It must be noted that all the patients with the CREST syndrome (6 cases) possessed Al-Ab.

Antilymphocyte Serum↗
PubMed1983

[Antinuclear, anti-DNA and anti-lymphocyte antibodies in systemic scleroderma. 62 cases].

The authors describe a prospective study of serum immunological abnormalities in 62 cases of systemic sclerodermia. Antinuclear antibodies were found in 67 percent of the cases. Contrary to expectation, the homogenous type was the most common. Anticentromeric antibodies were found in 4 of the 10 CREST syndrome patients. Anti-RNP (2/62) and natural anti-DNA antibodies are rarely found in sclerodermia. Non-cytotoxic anti-lymphocytic antibodies were found in more than half of the serums studied. They were frequently found in the CREST cases and in cases associated with Gougerot-Sjögren syndrome. Their significance is unknown. Lastly, almost all of the cases of systemic sclerodermia showed an immunological serum abnormality.

Antibodies, Antinuclear↗
PubMed1982

Chemokinetic activity of N-formyl-methionyl-leucyl-phenylalanine on human neutrophils, and its modulation by phenylbutazone.

Phenylbutazone (PBZ) is known to inhibit the oriented migration of human polymorphonuclear leukocytes (PMNs) induced by formyl-methionyl-leucyl-phenylalanine (FMLP), and to protect these cells against the deactivation caused by their prior incubation with FMLP. To gain insight into the mechanism of these effects, we measured the oriented PMN migration under agarose induced, in the presence and absence of PBZ, by FMLP, zymosan-activated serum and Klebsiella pneumoniae culture supernatant. The two components of this migration, i.e. the speed (chemokinesis), and direction of locomotion (chemotaxis), were also assessed. At concentrations ranging from 10(-8) to 10(-5) M, FMLP displayed similar chemotactic activity but the speed of PMN locomotion was maximal for 10(-7) M, and lower for concentrations above and below this level. Oriented migration was proportional to the mean cell locomotion speed during the experiments. PBZ inhibited both the oriented migration and locomotion speed induced by 10(-7) M FMLP, but did not affect its chemotactic activity. At concentrations of 10(-6) and 10(-5) M, PBZ increased oriented migration and locomotion speed, again without influencing FMLP chemotactic activity. Oriented migration induced by zymosan-activated serum was not affected by PBZ but the migration induced by Klebsiella pneumoniae culture supernatant diminished slightly. These results demonstrate that PBZ modulates the chemokinetic effect of FMLP on PMNs and thus alters oriented PMN migration.

Chemotaxis, Leukocyte↗
PubMed1981

[Role of Clostridium and its toxin in pseudo-membranous colitis (author's transl)].

At present many authors consider that pseudo-membranous colitis is of bacterial origin. The main pathogenic agent is Clostridium difficile. It is not easy to isolate this organism in the stool, selective media are under study. It liberates a lipo-glycoprotein exotoxin during lysis. It is only partially purified, its structure is not fully elucidated. Its molecular weight is not yet precisely determined. It consists of several polymerised polypeptide fragments of molecular weight 50 000. It is a thermolabile acid and alkaline sensitive cytotoxin which acts on the cell membranes and the ileo-caeco-colonic mucosa of man and animals. Clostridium difficile is transmissible by a small number of high risk carrier subjects who are potentially patients with pseudo-membranous colitis. Antibiotic therapy may lead to unbalance of the ecosystem represented by the bacterial flora of the digestive tract and favour the multiplication of a resistant strain to the administered antibiotic. The appearance of pseudo-membranous colitis requires the association of sufficient bacterial development (equal or greater than 10(7) germs per gram of stools) and the liberation of a cytotoxin. The pathogenic treatment consists of antibiotic therapy by Vancomycin or Metronidazole which seems, at present, the most active on the germs and a toxin absorbent, such as Cholestyramine, Coliptol hydrochloride or Heavy metals.

Animals↗