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P Cornacchione

Publications and source records attributed to P Cornacchione.

16 recordsLinked to original sources
PubMed2000

Group B Streptococcus induces apoptosis in macrophages.

Group B Streptococcus (GBS) is a pathogen that has developed some strategies to resist host immune defenses. Because phagocytic killing is an important pathogenetic mechanism for bacteria, we investigated whether GBS induces apoptosis in murine macrophages. GBS type III strain COH31 r/s (GBS-III) first causes a defect in cell membrane permeability, then at 24 h, apoptosis. Apoptosis was confirmed by several techniques based on morphological changes and DNA fragmentation. Cytochalasin D does not affect apoptosis, suggesting that GBS-III needs not be within the macrophage cytoplasm to promote apoptosis. Inhibition of host protein synthesis prevents apoptosis, whereas inhibition of caspase-1 or -3, does not. Therefore, GBS can trigger an apoptotic pathway independent of caspase-1 and -3, but dependent on protein synthesis. Inhibition of apoptosis by EGTA and PMA, and enhancement of apoptosis by calphostin C and GF109203X suggests that an increase in the cytosolic calcium level and protein kinase C activity status are important in GBS-induced apoptosis. Neither alteration of plasma membrane permeability nor apoptosis were induced by GBS grown in conditions impeding hemolysin expression or when we used dipalmitoylphosphatidylcholine, which inhibited GBS beta-hemolytic activity, suggesting that GBS beta-hemolysin could be involved in apoptosis. beta-Hemolysin, by causing membrane permeability defects, could allow calcium influx, which initiates macrophage apoptosis. GBS also induces apoptosis in human monocytes but not in tumor lines demonstrating the specificity of its activity. This study suggests that induction of macrophage apoptosis by GBS is a novel strategy to overcome host immune defenses.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Group B streptococci persist inside macrophages.

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In the early phase of infection, macrophages and polymorphonuclear cells (PMN) are the first immune cells that interact with GBS. In this in vitro study, to gain insight into GBS-macrophage interaction in the absence of type-specific antibodies, we examined the features of GBS survival in thioglycollate-elicited murine peritoneal macrophages and the effect of GBS on the protein kinase C (PKC)-dependent transduction pathway. Our results demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH 31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly in macrophages for up to 24 and 48 hr, respectively. However, macrophage activation by interferon-gamma (IFN-gamma) and lipopolysaccharide from Escherichia coli (LPS) caused a significant reduction in the time of intracellular persistence. Macrophage activation by IFN-gamma and LPS seems to be a multifactorial event involving multiple intracellular signal pathways also including PKC. Since PKC is one of the components in the signal network leading to macrophage activation and an important target for several intracellular micro-organisms, we wondered whether PKC could have a role in intracellular GBS survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate (PMA) for 18 hr and PKC inhibition by Calphostin C rendered macrophages more permissive for the intracellular GBS survival. Furthermore, GBS-infected macrophages were unable to respond to PMA and LPS, activators of PKC, by inducing antimicrobial activity. The ability of GBS to impair PKC-dependent cell signalling was also demonstrated by the reduced c-fos gene expression in GBS-infected macrophages with respect to control macrophages, after LPS stimulation. In conclusion, our results indicate that GBS survive in macrophages and impairment of PKC signal transduction contributes to their intracellular survival.

Animals↗
PubMed1998

Cytokine response to group B streptococcus infection in mice.

This study was undertaken to better understand the complex relationship between specific and non-specific host defence mechanisms and group B streptococci (GBS). A comprehensive kinetics analysis of cytokine mRNA expression was performed, by Northern blot assay, in peritoneal exudate cells (PEC) and spleen cells (SC) recovered from CD-1 mice at various times during the course of an intraperitoneal infection with a lethal dose (5 x 10(3) microorganisms/mouse) of type Ia GBS, reference strain 090 (GBS-Ia). Analysis of cytokines involved in the development of a specific TH response shows that GBS-Ia in PEC induce only a weak increase of IL-2 mRNA expression and in SC a cytokine pattern characterized by IL-2, IFN-gamma and IL-12 in the absence of IL-4, IL-5 and IL-10. This selected cytokine pattern could provide appropriate conditions for the development of a TH1 response. Analysis of inflammatory cytokines, which are usually induced early during an in vivo infection, shows that there is a significant expression of mRNA specific for IL-1beta, TNFalpha and IL-6, both in PEC and SC only at 24 h which persists at a high level until 36 h. This delayed cytokine induction, accompanied by the contemporary activation of splenic phagocytic cells, occurs only when the number of GBS-Ia is extremely high. In fact, at 24 h GBS-Ia have heavily colonized all organs. In vitro infection of thioglycollate-elicited peritoneal macrophages confirms that the ability of GBS-Ia to induce a strong inflammatory cytokine response depends strictly on the number of infecting microorganisms. Indeed, macrophages respond to GBS-Ia with a very rapid induction of IL-1beta and TNFalpha mRNA when infected at a ratio of 1:10, but not at 100:1. Two major observations emerged from this study: (1) GBS-Ia, by inducing a cytokine pattern which seems to favour development of a TH1 response, could evade antibody production essential for resistance to GBS; and (2) inflammatory cytokine response is induced when a heavy microbial invasion of the host has already occurred. These novel features of GBS-Ia could contribute to the development and progression of lethal infection in mice.

Animals↗
PubMed1996

Activation of cytokine genes during primary and anamnestic immune response to inactivated c. albicans.

Recent evidence suggests that after repeated stimulations with inactivated C. albicans (CA) cells, CD2F1 mice respond with a cytokine pattern typical of T-helper 1 (ThI) subset development. The purpose of this study was to analyse the sequence of immunological events which, soon after priming mice with CA, lead to the development of primary and anamnestic response. A comprehensive kinetics analysis of cytokine mRNA expression was performed by Northern blot assay, in peritoneal exudate cells (PEC), at different phases of immune response to CA: after priming (one i.p. injection of 2 x 10(7) CA cells mouse), during development of the primary immune response (five progressive CA i.p. injections over a 2-week period) and in the anamnestic response (CA booster 30 days after the primary response). In vitro assays were performed 2 and 24 hr after every CA stimulation. The response to CA priming was characterized by an early and high expression of interleukin-2 (IL-2) and IL-1 beta mRNAs At 24hr. IL-2 mRNA was still at a high level, while IL-1 beta had greatly decreased. A weak expression of IL-10 was only induced at 2 hr. whereas IL-12 p40 subunit, interferon-7 (IFN-7) IL-4 and IL-5 mRNAs were undetectable. In this phase no in vitro proliferative response of PEC to CA was observed, whereas a significant natural killer (NK) activity was induced. From the second CA injection, the IFN-7 mRNA was already induced at 2 hr. Its expression level increased progressively with the number of CA injections persisting up to 24 hr after the fifth stimulation. A progressive increase of IL-2 mRNA expression was also induced whereas IL-1 beta and IL-10 mRNAs were always transiently expressed at 2 hr at levels similar to those observed after the priming. IL-12 p40 subunit. IL-4 and IL-5 mRNAs were never detectable. The expression of this selected cytokine pattern typical of Thl response was correlated with the development of CA-specific T lymphocytes as confirmed by the in vitro proliferative response of CA-5d-induced PEC to CA. NK activity also increased progressively with the number of CA injections and after the fifth stimulation lymphokine-activated killer (LAK) activity was also induced. The anamnestic response to CA was characterized by a very quick induction of high levels of IL-2, II N-gamma and IL-1 beta mRNAs. IL-2 and IFN-gamma mRNAs remained high up to 24 hr while IL-1 beta mRNA decreased strongly. A weak, transient expression of IL-10 mRNA was induced at 2 hr whereas the IL-12 p40 subunit, IL-4 and IL-5 mRNAs were not detectable. The presence of CA-specific memory lymphocytes was confirmed by the in vitro specific proliferative response of PEC to CA. CA booster caused also a very rapid and high level of NK/LAK activation. In conclusion, these results indicate that CA is able to progressively trigger differential on of the Th1 subset which develops in the absence of IL-12, and that Th memory cells retain the same selected Th1 cytokine profile developed in the primary immune response.

Animals↗
PubMed1996

Activity inhibition of cytolytic lymphocytes by omeprazole.

This study examined the in vitro effect of omeprazole (OM) on various types of murine cytocidal lymphocytes. The results show that OM caused a strong inhibition of basal natural killer (NK) activity in spleen cells (SC) from untreated CD2F1 mice; in peritoneal exudate cells and SC activated in vivo by injection of maleic anhydride divinyl ether 1,2-copolymer (MVE-2) or inactivated Candida albicans (CA); in lymphokine-activated killer (LAK) activity generated in vitro from splenocytes cultured with rhIL-2 and in allo-specific cytotoxic lymphocyte-mediated lysis generated in vitro. A significant inhibition of cytotoxic activity of all types of effector cells after 30 min incubation was already induced by OM at 1 x 10(-3) M concentration, after 1 h incubation at 5 x 10(-4) M and after 4 h incubation at 1 x 10(-4) M OM. Complete inhibition of lytic activity was obtained after 4 h incubation of effector cells with 1 x 10(-3) M OM. No inhibitory effect was observed at 5 x 10(-5) M OM concentration. Indomethacin did not abrogate the OM inhibitory effect on NK/LAK activity, suggesting that prostaglandins are not involved in the process leading to suppression of cytocidal activity. When effector cells were incubated with OM in presence of rhIL-2 (500 U/ml), the cytokine failed to antagonize the inhibitory effect of the drug. On the contrary, if OM pretreated cells were incubated with rhIL-2 for a further 18 h after drug removal, this cytokine was able to restore NK activity, but only when NK inhibition was incomplete. These results demonstrate for the first time that in vitro OM causes a rapid, strong effect on various types of cytotoxic lymphocytes ranging from cytotoxicity inhibition to irreversible cell damage.

Animals↗
PubMed1995

Cytokine response to inactivated Candida albicans in mice.

Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effectors in mice. In the present study we examined the expression of cytokine genes involved in the immune response to CA. It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response. Northern blot analysis was performed on peritoneal exudate cells (PEC) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days -14, -10, -7, -3, 0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0). On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity. Two hours after CA-5d a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased. IL-6, TNF alpha, and IL-2R alpha chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed. IL-12 mRNA was also absent in earlier stages of the CA sensitization. Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0. At 24 hr whereas IL-2 mRNA remained high, both IL-1 beta and IFN gamma mRNAs expression had decreased. Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced. After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1 beta mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFN gamma and IL-2, cytokines involved in the development of TH1 response but it is unable to induce IL-12. This secondary pathway, without IL-12 involvement in the development of TH1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells.

Animals↗
PubMed1995

Local and systemic immune response to inactivated Candida albicans in mice.

To improve our understanding of the role natural-immunity cells play in regulating the immune response to Candida albicans (CA) we compared local versus systemic effects of intraperitoneal inoculations with inactivated CA cells in mice. Peritoneal exudate cells (PECs) and spleen cells (SCs) were recovered from CD2F1 mice after 5 intraperitoneal CA injections (2 x 10(7) cells/mouse on days -14, -10, -7, -3 and 0 (CA-5d) with respect to in vitro assays performed at 2 h, 24 h, 3 days and 5 days). Northern blot analysis revealed that 2 h after CA-5d, PECs expressed a high level of IL-2, IFN-gamma, IL-1 beta and a low level of IL-10 and TNF-alpha mRNAs, while IL-4 and IL-5 mRNAs were absent, suggesting the development of TH1 subset. At 24 h, while IL-2 mRNA remained high, IL-1 beta and IFN-gamma expression had decreased and IL-10 and TNF-alpha mRNAs were no longer detectable. Instead, in spleens of CA-treated mice, examined up to 5 days after CA-5d, only IL-2 and IL-1 beta mRNAs were detectable, but the expression level was similar to that of untreated control mice. CA-5d induced a high level of natural-killer (NK)/lymphokine-activated-killer (LAK) activity in the peritoneal cavity but did not affect spleen NK activity. After CA-5d, the proliferative response of PECs to mitogens and CA antigens was also different from that of SCs. Unfractionated PECs were unable to proliferate in response to concanavalin A (Con A), IL-2, CA cells and CA cell wall mannoprotein, but after removal of the nylon-wool-adherent fraction, the nonadherent peritoneal cells (Nad-PECs) showed a significant proliferative response to mitogens. After depletion of NK cells by anti-asialo-GM1 antibody plus complement, the proliferative response of Nad-PECs to Con A and CA increased further. Contrary to the PEC response, unfractionated SCs from the same animals responded very well to mitogens and CA antigens and the proliferative response was significantly higher compared to that of SC from control mice. In conclusion, these results cast some light on the mechanisms by which NK cells and macrophages regulated the development of the local specific response to CA: activated NK cells, by producing IFN-gamma, favor the development of TH1 subset, while suppressor macrophages keep proliferation of T lymphocytes under control because of the presence of highly activated NK cells.

Animals↗
PubMed1994

Induction and persistence in vivo of NK/LAK activity by a mannoprotein component of Candida albicans cell wall.

In a previous study we demonstrated that NK/LAK effectors are quickly induced in the peritoneal cavity of CD2F1 mice by a booster dose with inactivated Candida albicans (CA) cells or by the purified cell wall mannoprotein (MP), for a long time after CA sensitization. In this study we investigated the immunologic nature and kinetics of early events of the booster phenomenon. Intraperitoneal inoculation of CA in CD2F1 mice, 30 days after pretreatment with five doses of CA (2 x 10(7) cells/mouse) over a 2-week period (CA-5d treatment), elicited a very rapid recruitment of asialo GM1+ cells, L3T4+ cells, and Ly 2+ cells. Asialo GM1+ cells and Ly 2+ cells reached a maximum number 12 hr after the booster dose, while L3T4+ cells reached the maximum after 24 hr. The number of L3T4+ cells was about twofold greater than Ly 2+ cells at all times tested. A similar kinetic pattern was found after MP booster. In C57BL/6 mice we confirmed that CA and MP boosters induced LGL which express a NK antigen, detected by 3A4 mAb, and the activation marker CD25. The peak of non-MHC-restricted PEC cytotoxicity, which was reached 24 hr after MP or CA booster, did not correspond to the time (12 hr) for maximum number increase of asialo GM1+ cells and 3A4+ cells. Two hours after CA or MP booster in PEC there was a rapid and strong increase of IL-2 mRNA expression, which persisted at a high level 24 hr after booster. In CA-5d-pretreated mice, a persistent NK/LAK-like activity in the peritoneal cavity can be maintained by boosters with MP administered every 3 days. Such treatment, which we performed up to 15 days after CA sensitization, rendered the mice more responsive to further MP boosters. Effects of CA were not restricted to the peritoneal compartment because (a) there was a rebound of splenic NK activity about 10 days after CA-5d treatment by ip route and (b) CA given by iv route significantly increased splenic NK activity up to 15-20 days after CA-5d treatment. Recombinant human interleukin 2 (rhIL-2), given ip to mice (1000 U/mouse) in combination with CA during CA-5d treatment and with MP in the booster, strongly increased the level of peritoneal NK/LAK activity and PEC cellularity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Antibody-independent protection in mice against type Ia group B streptococcus lethal infection.

There is ample evidence that protection against group B streptococcal (GBS) disease, both in experimental animals and in humans, is related to the presence of specific antibodies and complement. However, until now the possibility of increasing resistance to GBS infection by potentiating natural cell-mediated immunity in the host, has not been explored. In this study we examine the effect of administering in vivo MVE-2 (a polymer fraction of 1,2-co-polymer of divinyl ether and maleic anhydride) and inactivated Candida albicans (CA) cells on mouse resistance to the reference strain type Ia 090 GBS (GBS-090) lethal infection. MVE-2 and CA, respectively a synthetic and a microbial biological response modifier (BRM), are strong inducers and activators of natural resistance effectors, such as natural killer (NK) cells, macrophages and polymorphonuclear cells (PMN). The results showed that MVE-2 protected 100% CD-1 mice from a systemic lethal challenge with GBS-090 (5 x 10(3) microorganisms/mouse) when administered 3 days before infection at dose of 50 mg kg-1. CA treatment, in five doses (CA-5d) over 14 days protected 100% mice when administered at 2 x 10(7) cells/mouse and when the last CA injection was given 1 day before the GBS-090 challenge. Instead, when the GBS-090 challenge was performed by intraperitoneal route, protection was obtained with CA-5d treatment but not with MVE-2. The possibility that MVE-2 or CA stimulated a rapid production of specific antibodies against GBS-090 infection was excluded by the ELISA assay. Evidence exists that NK cells do not play a primary role as effectors in the MVE-2 and CA conferred protection since the strong reduction in NK activity, due to in vivo administration of anti-asialo GM1 antibodies before GBS-090 infection, did not influence the BRM-induced protection. Besides, high NK activity levels, induced by in vivo rhIL-2 administration, did not protect the mice against GBS-090 infection. Both studies on in vivo clearance and in vitro microbicidal activity, showed that, after 1 h, immunopotentiated effectors were unable to kill GBS-090, but were highly effective against GBS type VI. These results seem to indicate that intracellular GBS-090 killing is a slow process requiring more than 1 h. This study demonstrates that it is possible to increase resistance to GBS-090 lethal infection by BRMs, by potentiating the antibody-independent microbicidal activity of the phagocytes.

Animals↗
PubMed1992

In vivo modulation of lymphokine-activated killer cell activity by cell wall components of Candida albicans.

We have previously reported that inoculating CD2F1 mice intraperitoneally with five doses of 2 x 10(7) inactivated Candida albicans (CA) cells was associated with the induction of lymphokine-activated killer (LAK)-like effectors. In this study we investigated the ability of some purified cell wall components of CA (CA-CW) to induce LAK-like cells in vivo. Multiple administrations of glucan ghost (GG), a mannoprotein mixture (MP) and a low-protein mannan fraction (M) at variance with whole CA did not induce LAK-like cells in the peritoneal cavity. However, the broad-spectrum antitumor cytotoxicity induced by CA could be recalled to a high level by a booster dose of MP and M, but not GG, given up to 70 days after the multiple CA-treatment. This induced cytotoxicity was maximum when the booster was given on Day +14 after CA-treatment and minimum on Day +70. In CA-treated mice, inoculated on Day +30 with CA or MP, LAK-like cytotoxicity was already significantly increased 4 hr after the booster, but the maximum value was reached at 24 hr. Anti-mannan antibodies did not interfere with LAK-like cells induction by CA because splenectomy before CA-treatment or passive administration of anti-mannan antibodies had no effect on the rapid activation of cytotoxicity by CA or a booster dose of MP. Administration of recombinant human interleukin-2 (rhIL-2) to CA-treated mice induced a higher level of NK activity than that induced by the same dose in untreated control mice, but did not activate LAK-like effectors. The results indicate that LAK-like effectors are easily generated in the peritoneal cavity by a booster with a defined antigenic constituent of CA cell wall for a long period in CA-sensitized mice.

Animals↗
PubMed1990

Induction of LAK-like cells in the peritoneal cavity of mice by inactivated Candida albicans.

We have investigated the effect of multiple administrations of inactivated Candida albicans (CA) cells on induction of non-MHC-restricted antitumor cytotoxic responses both in normal and congenitally athymic (nude) mice. Intraperitoneal inoculation of CD2F1 mice with five doses of 2 x 10(7) CA cells over a 2-week interval was associated with the induction of peritoneal exudate cells (PEC) that mediated natural killer cell activity. These cells, in contrast to those elicited by a single dose of CA, killed both NK-sensitive and NK-resistant tumor target cells in vitro. This broad-spectrum, antitumor cytotoxicity peaked 1 day after the last injection of CA, and decreased to control values within 6 (NK-resistant) or 14 (NK-sensitive target cells) days. Cytotoxicity could be recalled to a high level by a boosting injection of CA or a major mannoprotein-soluble antigen (MP) from the Candida cell wall, given 30 days after multiple CA treatment. Upon a 24-hr in vitro incubation, CA-induced peritoneal immunoeffectors lost their killing activity unless human recombinant interleukin-2 (rIL-2) was added to cultures. The non-MHC-restricted cytotoxic PEC activity induced by CA was mainly associated with nonadherent, nonphagocytic large granular lymphocytes (LGL) which exhibited the following phenotypes: (i) asialo GM1+, Lyt 2.2-, and partially Thy 1.2+ (effectors active against NK-sensitive targets) and (ii) asialo GM1+, Lyt 2.2-, and Thy 1.2+ (effectors active against NK-resistant targets). Nude mice also responded to multiple CA inoculations by displaying high cytotoxic activity against NK-sensitive targets and significant cytotoxicity against NK-resistant targets. This cytotoxicity could be recalled on Day +30, and the cytotoxic effectors involved were highly sensitive to anti-asialo GM1 plus complement treatment. Overall, the results add further experimental evidence to the wide range of immunomodulatory properties possessed by C. albicans, and demonstrate that the majority of antitumor cytotoxic activity induced by fungal cells was due to lymphokine-activated killer (LAK)-like effectors.

Animals↗
PubMed1990

Experimental model of type IV Streptococcus agalactiae (group B streptococcus) infection in mice with early development of septic arthritis.

We have established an experimental murine model to gain insight into the pathogenicity and clinical features of type IV group B streptococcus (GBS) infections. Adult CD-1 mice were challenged intravenously with 10(7) type IV GBS cells, inducing systemic invasion. Most of the animals were able to clear the infection from the blood, brain, and lungs within 2 weeks and from the spleen and liver within 1 month. However, the animals were unable to clear the microorganism from the joints and kidneys during the 60-day observation period. About 80% of the mice challenged intravenously with type IV GBS manifested early septic arthritis, which evolved from an acute exudative synovitis to permanent lesions characterized by irreversible joint damage and ankylosis. Induction of persistent septic arthritis was dependent on the number and viability of microorganisms inoculated and was unrelated to the strain of type IV GBS and the growth phase of the inoculum. Type-specific antibodies of both immunoglobulin M and G classes could be detected by agglutination and enzyme-linked immunosorbent assay from days 7 and 14, respectively; immunoglobulin G antibodies persisted for more than 40 days. Complexes of antibodies and group- and type-specific antigens were detected in mouse sera 24 h after infection and persisted up to day 22. These results were obtained an experimental model of type IV GBS chronic infection with early development of septic arthritis, which could be useful in future studies of pathogenicity and immune mechanisms involved in the host resistance to this microorganism.

Animals↗
PubMedDate not supplied

A rapid Candida albicans hyphal-form growth inhibition assay: determination of myelomonocytic-mediated antifungal activity.

An in vitro microassay for the measurement of Candida albicans hyphal-form growth inhibition by myelomonocytic cells is described. The assay is rapid, easy-to-perform and objective. A Candida strain capable of in vitro dimorphic transition from yeast to hyphal form has been employed. The assay is based on the incorporation of 3H-glucose by the fungus, the effect being dependent upon the time of pulse, size of the inoculum and concentration of radiolabelled metabolite. In particular, C. albicans hyphal form, obtained by a 3 h incubation in vitro in the presence of 10% fetal calf serum, is co-incubated with the effector cells. A pulse with 3H-glucose in water is then performed and the radioactivity incorporated by the residual Candida is taken as an indication of hyphal growth. We found that polymorphonuclear cells, peritoneal macrophages and the cloned GG2EE macrophage cell line significantly inhibited hyphal growth, the effects being time and effector-to-target cell ratio dependent.

Animals↗
PubMedDate not supplied

In vitro effects of meropenem and imipenem/cilastatin on some functions of human natural effector cells.

Meropenem, a new carbapenem antibiotic, was assessed to evaluate its effects on some functional parameters of human polymorphonuclear (PMN) and natural killer (NK) cells in comparison with imipenem/cilastatin. Both drugs significantly inhibited PMN phagocytosis and chemotaxis at concentrations of 2,000 and 4,000 microg/ml. They affected PMN microbicidal activity, evaluated against Candida albicans, only at 4,000 microg/ml. A study of the effects of both drugs on peripheral NK populations and the human NK line (NK-92) showed that even at 4,000 microg/ml there was no effect on antitumor activity. These data indicate that meropenem can reduce some PMN antimicrobial functions only at very high concentrations like imipenem/cilastatin, whereas no concentration influenced NK activity.

Candida↗
PubMedDate not supplied

Omeprazole induces apoptosis in jurkat cells.

We report for the first time a potent apoptotic effect of omeprazole (OM). Apoptosis was induced in Jurkat cells in a time and concentration-dependent mode. Caspase 3 and PARP were rapidly cleaved in response to OM, but apoptosis was only partially inhibited by the caspase 3 inhibitor DEVD-CHO. OM also induced an early lysosomal destabilization which increased progressively and was correlated with a parallel increase in apoptotic cells. The cysteine protease inhibitor E64d gave strong protection against apoptosis thus proving the involvement of lysosomal enzymes in OM-induced apoptosis whereas, it did not impede the caspase 3 cleavage. Instead ZVAD-fmk, a general caspase inhibitor, also able to inhibit cathepsin activity, protected cells completely from OM-induced apoptosis. It therefore seems that both caspases and cysteine cathepsins are involved in the execution stage of OM-induced apoptosis.

Anti-Ulcer Agents↗