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R van Furth

Publications and source records attributed to R van Furth.

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

Endogenous interleukin-4 does not suppress the resistance against a primary or a secondary Listeria monocytogenes infection in mice.

Interleukin-4 (IL-4), a cytokine produced by T-helper 2 (Th2) cells, can inhibit the development of T-helper 1 (Th1) cells, which results in a decreased release of cytokines by the latter. As interferon-gamma (IFN-gamma), produced by Th1 cells, is involved in the resistance against a Listeria monocytogenes infection, the role of endogenously formed IL-4 during a Listeria infection in mice was investigated. Neutralization of endogenously formed cytokines by subcutaneously injected alginate-encapsulated monoclonal antibody (MoAb)-forming cells results in high antibody titres in the circulation over a long time period. The aim of the present study was to reevaluate the effect of neutralization of IL-4 during a primary Listeria infection and to investigate the role of IL-4 during a secondary infection in mice using encapsulated MoAb-forming cells. During the course of a primary infection in mice given anti-IL-4 antibody-forming cells (anti-IL-4-FC), the number of Listeria found in the liver and spleen was comparable to that found in control mice given anti-beta-galactosidase antibody-forming cells (anti-beta-gal-FC). Activation of macrophages measured by inhibition of Toxoplasma gondii proliferation and the release of reactive nitrogen intermediates (RNI) was not affected by anti-IL-4-FC treatment during infection. Furthermore, during a secondary L. monocytogenes infection the number of bacteria in the liver and spleen of anti-IL-4-treated immune mice was comparable to anti-beta-gal-FC-treated, control, immune mice. The concentration of IFN-gamma in plasma of anti-IL-4-treated immune mice was similar to that of control immune mice. Taken together, these findings demonstrate that neutralization of endogenously formed IL-4 does not affect resistance to a primary or a secondary L. monocytogenes infection in mice.

Animals↗
PubMed1998

Reduced toxoplasmastatic activity of monocytes from AIDS patients: a role for granulocyte-macrophage colony-stimulating factor.

In the present study the role of granulocyte-macrophage colony stimulating factor (GM-CSF) in the reduced toxoplasmastatic activity of monocytes was investigated in patients with acquired immunodeficiency syndrome (AIDS). The secretion of GM-CSF by non-stimulated monocytes and by Toxoplasma gondii-infected monocytes from AIDS patients did not differ from that of healthy individuals. Furthermore, GM-CSF was not detected in sera from AIDS patients and healthy individuals. However, upon stimulation with lipopolysaccharide (LPS), monocytes from AIDS patients released significantly more GM-CSF than those from healthy individuals. Incubation of monocytes from AIDS patients with polyclonal antibodies against GM-CSF restored their inhibitory activity against T. gondii. On the basis of the present and earlier results the putative mechanism of reduced toxoplasmastatic activity of monocytes from AIDS patients may be as follows: upon stimulation with human immunodeficiency virus (HIV) the increased synthesis of GM-CSF by monocytes stimulates the production of prostaglandin E2 (PGE2) which, in turn, impairs the toxoplasmastatic activity of these cells.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Infection of human vascular endothelial cells with Staphylococcus aureus induces hyperadhesiveness for human monocytes and granulocytes.

The consequences of internalization of Staphylococcus aureus by HUVEC with respect to their adhesiveness for human monocytes and granulocytes were investigated. Viable and UV-killed, but not heat-killed, S. aureus were internalized by HUVEC, which required participation of the endothelial cytoskeleton. S. aureus-infected HUVEC displayed increased surface expression of CD106 (VCAM-1), CD54 (ICAM-1), and MHC I molecules. Expression of CD62P (P-selectin), CD62E (E-selectin), CD31 (PECAM-1), and CD102 (ICAM-2) was not affected. Concomitantly, these HUVEC expressed a time- and inoculum size-dependent hyperadhesiveness for monocytes and granulocytes. Monocyte adhesion reached maximal levels (approximately 60% adhesion) 23 h after the initial 1 h period of infection of HUVEC with about 50 bacteria per single HUVEC. To induce maximal (approximately 20%) adhesion of granulocytes, five times higher concentrations of HUVEC-infecting bacteria were required. Using the appropriate mAb, granulocyte adhesion to S. aureus-infected HUVEC was shown to be entirely mediated by the beta2 (CD11/CD18) integrins. Monocyte adhesion to these HUVEC was largely (approximately 70%) dependent on both CD11a/CD18 (LFA-1) and CD49d/CD29 (VLA-4). This demonstrates that infection of HUVEC with S. aureus potentiates CD11/CD18-mediated granulocyte adhesion and shifts the mechanism of monocyte adhesion from being completely CD11/CD18 dependent to one that also utilizes the VLA-4/VCAM-1 dependent pathway. Together, these findings indicate that in response to internalization of S. aureus, vascular endothelial cells may initiate recruitment of monocytes and granulocytes, which may be an important initial event in the pathogenesis of endovascular diseases.

Cell Adhesion↗
PubMed1997

Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-alpha, IL-1 beta IL-10 by human leucocytes.

The present study concerns the effect of the xanthine derivates lisofylline (LSF) and pentoxifylline (PTX) on the production of pro-inflammatory cytokines tumour-necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and the de-activating cytokine interleukin-10 (IL-10) by human leucocytes during stimulation with lipopolysaccharide (LPS), heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteria (GPB). The production of TNF-alpha and IL-1 beta by leucocytes stimulated with LPS, Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae was inhibited by both drugs. The production of IL-10 by leucocytes stimulated with LPS and Hib was inhibited by both xanthine derivates only at 48 hr. However, incubation of leucocytes with S. pneumoniae in the presence of LSF or PTX stimulated the production of IL-10 about four- and twofold at 24 hr and 48 hr, respectively. In all instances, the extent of inhibition or enhancement of cytokine production by LSF or PTX was equal. The divergent effects of xanthine derivates on the IL-10 production indicate the existence of distinct intracellular pathways depending on whether leucocytes are stimulated by GPB or GNB.

Antigens, Bacterial↗
PubMed1997

Difference in binding of killed and live Streptococcus pneumoniae serotypes by C-reactive protein.

The binding and opsonic properties of C-reactive protein (CRP) for various species of bacteria were investigated. CRP bound more avidly to killed than to live Streptococcus pneumoniae, the binding varying among various serotypes; CRP hardly bound to a number of other bacterial species studied. CRP enhanced complement-dependent phagocytosis of live S. pneumoniae by granulocytes but did not enhance the phagocytosis of live Staphylococcus aureus or group B streptococci. We suppose that CRP may serve as an opsonin for killed bacteria and bacterial debris but is probably not an important opsonin for live bacteria other than S. pneumoniae.

Adult↗
PubMed1997

Antibody response to Haemophilus influenzae type b vaccine in relation to the number of CD4+ T lymphocytes in adults infected with human immunodeficiency virus.

A prospective study of antibody production by adults infected with human immunodeficiency virus (HIV) after vaccination with tetanus toxoid-conjugated Haemophilus influenzae type b (Hib) vaccine was conducted. Concentrations of antibodies to the two immunogenic components of the vaccine (i.e., polyribosylribitolphosphate [PRP] and tetanus toxin) were determined. Individuals were divided into three groups according to the CD4+ T lymphocyte count: group 1, < or =100 x 10(6)/L; group 2, 101-300 x 10(6)/L; and group 3, >300 x 10(6)/L. After vaccination, concentrations of IgM and IgG antibodies to PRP were significantly lower in group 1 than in the other patient groups and controls. A CD4+ T lymphocyte count of <100 x 10(6)/L and an impaired proliferative response of lymphocytes to monoclonal antibody to CD3 were independently associated with a less than threefold increase in concentrations of IgG antibody to PRP. Analysis of IgG subclasses demonstrated that the production of IgG1 antibodies was predominantly affected. Postvaccination concentrations of antibody to tetanus toxin were significantly lower in group 1 than in group 3 and controls. Both prevaccination and postvaccination concentrations of antibody to tetanus toxin were not correlated with the magnitude of the response of antibody to PRP. We conclude that HIV-infected individuals with CD4+ T Iymphocyte counts of <100 x 10(6)/L demonstrate an impaired antibody response after vaccination with conjugated Hib vaccine.

Adolescent↗
PubMed1997

Elimination of resident macrophages from the livers and spleens of immune mice impairs acquired resistance against a secondary Listeria monocytogenes infection.

During a secondary Listeria monocytogenes infection in mice, the bacteria are eliminated more rapidly from the liver and spleen than during a primary infection. This acquired resistance against a secondary infection is dependent on T lymphocytes, which induce enhanced elimination of bacteria via stimulation of effector cells such as neutrophils, resident macrophages, exudate macrophages, and hepatocytes. The aim of the present study was to determine the role of the resident macrophages in acquired resistance against a secondary L. monocytogenes infection in mice. Mice which had recovered from a sublethal primary infection with 0.1 50% lethal dose (LD50) of L. monocytogenes intravenously (i.v.), i.e., immune mice, received a challenge of 1 LD50 of L. monocytogenes i.v. to induce a secondary infection. At 2 days prior to challenge, immune mice were given an i.v. injection of liposomes containing dichloromethylene-diphosphonate (L-Cl2MDP) to selectively eliminate resident macrophages from the liver and spleen. Control immune mice received either phosphate-buffered saline (PBS) or liposomes containing PBS (L-PBS). Treatment of mice with L-Cl2MDP effectively eliminated resident macrophages from the liver and spleen but did not affect the number of granulocytes, monocytes, or lymphocytes in peripheral blood or their migration to a site of inflammation. Phagocytosis and killing of L. monocytogenes by peritoneal exudate cells elicited with heat-killed L. monocytogenes were similar in all groups of immune mice. On day 3 of a secondary infection, the number of L. monocytogenes organisms in the livers and spleens of L-Cl2MDP-treated immune mice was 4 log10 units higher than in immune mice treated with PBS or L-PBS. The concentration of reactive nitrogen intermediates in plasma, a measure of the severity of infection, was 70-fold higher for L-Cl2MDP-treated immune mice than for PBS- or L-PBS-treated immune mice. Treatment with L-Cl2MDP significantly increased the number of inflammatory foci in the liver and spleen, decreased their size, and affected their structure. From these results, we conclude that resident macrophages are required for the expression of acquired resistance against a secondary L. monocytogenes infection in mice.

Animals↗
PubMed1996

Heat shock protein 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes.

Expression of members of the heat shock protein 60 (hsp60) family in tissues has been reported to coincide with leukocyte infiltration, but it is not known whether these proteins are directly involved in the extravasation of leukocytes. Extravasation of leukocytes requires their adhesion to endothelial cells (EC) via an interaction between adhesion molecules expressed on both cell types. The aim of the present study was to investigate the effect of recombinant mycobacterial hsp65 on the adhesive characteristics of EC for monocytes and granulocytes. Incubation of EC with hsp65 induces a concentration- and time-dependent increase in adhesiveness of these EC for monocytes and granulocytes. The effect was maximal after incubation of EC with hsp65 for 4 to 6 h. In addition, incubation of EC with hsp65 induced the expression of endothelial CD62E (E-selectin), CD106 (vascular cell adhesion molecule-1) and CD54 (intercellular adhesion molecule-1). The increased adhesion of granulocytes to hsp65-stimulated EC was inhibited completely by blocking Ab against CD62E. mAb against endothelial CD62E, CD106, or CD54 or against the monocyte adhesion molecules CD14 or CD49d (very late Ag-4) did not inhibit the increased adhesion of monocytes to hsp65-stimulated EC; however, mAb against the monocyte adhesion molecule CD18 (beta2-integrin) inhibited monocyte adhesion to hsp65-stimulated EC to the same extent as monocyte adhesion to nonstimulated EC. Hsp65 did not exert its effect in an autocrine or paracrine fashion via the endogenous production of IL-1, TNF-alpha, or other factors or via contaminating LPS. Together these results indicate that hsp65 can play an important role in the adhesion of monocytes and granulocytes to EC at sites of inflammation via modulation of the adhesive characteristics of EC and thus may facilitate extravasation of these phagocytes.

Antigens, CD↗
PubMed1996

Effect of granulocyte colony-stimulating factor on the course of infection with gram-positive bacteria in mice during granulocytopenia induced by sublethal irradiation or cyclophosphamide.

This study assesses the effect of granulocyte colony-stimulating factor (G-CSF) on the outcome of infection with Listeria monocytogenes or Staphylococcus aureus in mice during leukocytopenia induced by sublethal total body irradiation or cyclophosphamide treatment. The role of granulocytes during infection was assessed in the thigh muscle, spleen, and liver. G-CSF treatment in naive mice increased the number of blood granulocytes; upon infection, these numbers increased further, but G-CSF did not affect the outgrowth of bacteria in the tissues. Cyclophosphamide treatment and sublethal irradiation decreased the number of blood granulocytes, which was not affected by G-CSF treatment. However, during infection in cyclophosphamide-treated mice, G-CSF increased the number of granulocytes in the circulation and at the site of infection and decreased the number of bacteria in the tissues. Treatment with G-CSF did not affect the number of granulocytes or the course of infection in irradiated mice.

Agranulocytosis↗
PubMed1996

Acquired resistance against a secondary infection with Listeria monocytogenes in mice is not dependent on reactive nitrogen intermediates.

During an infection, inflammatory mediators can induce the production of nitric oxide, a reactive nitrogen intermediate (RNI) which plays a role in antimicrobial activity against a wide variety of pathogens. In vitro experiments have shown that release of RNI by macrophages is mediated by tumor necrosis factor alpha (TNF). Since TNF is essential for acquired resistance during a secondary Listeria monocytogenes infection in mice, the aim of the present study was to determine whether RNI are also involved in the course of such an infection. Mice which had recovered from a sublethal primary infection with 0.1 50% lethal dose of (LD50) L. monocytogenes were infected intravenously with 10LD50 of L. monocytogenes. During a primary infection, the number of bacteria in the liver and spleen, as well as the concentration of RNI in plasma, increased. During a secondary infection, the number of bacteria in the liver and spleen decreased whereas no significant increase in the concentration of RNI in plasma was observed. Neutralization of endogenously produced TNF and gamma interferon by subcutaneous injection of alginate-encapsulated monoclonal antibody-forming cells during a secondary infection resulted in an increase in the number of bacteria in the liver and spleen an increase in the concentration of RNI in plasma. When the production of RNI was inhibited by treatment of mice with competitive NO-synthase inhibitor N omega-nitro-L-arginine methyl ester hydrochloride (L-Name) and an iota-arginine-deficient diet during a secondary infection, the proliferation of L. monocytogenes in the liver and spleen was not affected whereas the concentration of RNI in plasma of these mice was significantly reduced. Our findings that inhibition of RNI formation during a secondary infection does not affect the proliferation of L. monocytogenes in the liver and spleen and that enhanced elimination of bacteria from these organs is not accompanied by an increase in the concentration of RNI in plasma led to the conclusion that resistance against a secondary infection with L. monocytogenes is not dependent on RNI.

Animals↗
PubMed1996

Role of YadA in resistance to killing of Yersinia enterocolitica by antimicrobial polypeptides of human granulocytes.

The virulence plasmid pYVe of Yersinia enterocolitica codes for the production of the outer membrane protein YadA and the secretion of several proteins, called Yops, which may protect this bacterium against killing by human granulocytes. Granulocytes kill ingested microorganisms by oxygen-dependent and oxygen-independent mechanisms, the latter including antimicrobial polypeptides. The aim of this study was to determine whether virulent (pYVe+) Y. enterocolitica and plasmid-cured avirulent (pYVe-) Y. enterocolitica differ in susceptibility to antimicrobial polypeptides extracted from granules of human granulocytes. The acetic acid granule extract contained several polypeptides with antimicrobial activity against Y. enterocolitica as determined by gel overlay and radial diffusion assays. Two of these polypeptides were identified as lysozyme and defensins. pYVe+ Y. enterocolitica was less susceptible than pYVe- Y. enterocolitica to the antimicrobial activity of granule extract, lysozyme, and defensins as determined in a suspension assay, which indicated that the pYVe plasmid mediates a reduced susceptibility to these polypeptides. The role of YadA in the resistance to antimicrobial polypeptides was analyzed by using mutants of Y. enterocolitica that specifically lack or express YadA. The results demonstrated that YadA conferred resistance to the killing of Y. enterocolitica by the granule extract. Together, these results indicate that the plasmid-encoded factor YadA contributes to the resistance of Y. enterocolitica to the killing by antimicrobial polypeptides of human granulocytes.

Adhesins, Bacterial↗
PubMed1996

Increased production of nitric oxide correlates with viral load and activation of mononuclear phagocytes in HIV-infected patients.

The objective of our study was to determine the production of nitric oxide (NO) in patients infected with human immunodeficiency virus (HIV) and its relation to cellular immunity, activation of mononuclear phagocytes and the amount of circulating virus. Therefore, serum nitrate, the stable metabolite of NO, the number of peripheral CD4+ T-lmphocytes, serum neopterin, plasma HIV-RNA and HIV-DNA in peripheral blood mononuclear cells of afebrile HIV-infected patients were determined. Serum nitrate levels were significantly (p = 0.002) increased in HIV-infected patients (median 37 microM, range 13-137 microM, n = 77) in comparison to healthy subjects (median 28 microM, range 21-40 microM, n = 17). Serum nitrate levels did not correlate with the number of CD4+ T-lymphocytes (r = 0.05, p > 0.05). Serum nitrate levels were positively correlated with neopterin (r = 0.36, p = 0.05, n = 30), the amount of HIV-DNA in peripheral blood mononuclear cells (r = 0.63, p < 0.001, n =27) and plasma HIV-RNA levels (r = 0.35, p = 0.08, n = 27). A possible explanation of our findings is that HIV induces the production of NO by means of activated mononuclear phagocytes.

Adult↗
PubMed1995

Binding of FimD on Bordetella pertussis to very late antigen-5 on monocytes activates complement receptor type 3 via protein tyrosine kinases.

Nonopsonized Bordetella pertussis bind to human monocytes by means of the virulence factors filamentous hemagglutinin (FHA), pertactin, and the minor fimbrial subunit FimD. Receptors on monocytes that mediate binding of B. pertussis to these cells include complement receptor type 3 (CR3), which binds to FHA of B. pertussis, and very late antigen-5 (VLA-5), which binds to an, as yet, unknown ligand on these bacteria. In the present study, the possibility that FimD acts as a ligand for VLA-5 was investigated. Soluble fibronectin, which is the natural ligand for VLA-5, or mAbs against VLA-5 inhibited binding to monocytes of B. pertussis strains that express FimD but not of mutant strains that lack FimD. Beads that were coated with the fusion protein maltose-binding protein-FimD bound to adherent monocytes, and this binding was inhibited by soluble fibronectin or mAb against the alpha- or beta-chain of VLA-5, while soluble collagen or mAb against VLA-4, VLA-6, CR3, or HLA class II had no effect. Down-modulation of VLA-5 on the apical surface of monocytes by plating the cells onto surfaces precoated with anti-VLA-5 mAb also inhibited binding of beads coated with maltose-binding protein-FimD to monocytes, while precoating of the surfaces with mAb against VLA-6 or CR3 had no effect. These results indicate that VLA-5 on monocytes serves as a receptor for FimD on B. pertussis. Binding of C3bi-coated erythrocytes to monocytes, which is a measure of the binding activity of CR3, was enhanced when monocytes were adhered onto plates precoated with purified fimbriae of B. pertussis, while precoating with fimbriae lacking FimD had no effect. Precoating of the plates with FimD-containing fimbriae also enhanced binding of B. pertussis, which express FHA, but not of strains that lack FHA, to monocytes. The enhanced binding of C3bi-coated erythrocytes and B. pertussis to monocytes could be markedly inhibited by tyrphostin-47, a protein tyrosine kinase inhibitor. These results demonstrate that interaction of FimD of B. pertussis with VLA-5 on monocytes activates CR3, which requires protein tyrosine kinases and results in enhanced binding of B. pertussis to the latter receptor via FHA.

Bacterial Adhesion↗
PubMed1995

Role of protein kinase C isozymes in Fc gamma receptor-mediated intracellular killing of Staphylococcus aureus by human monocytes.

Intracellular killing of Staphylococcus aureus by human monocytes after cross-linking Fc gamma R is known to be a phospholipase C (PLC)-dependent process. Activation of PLC leads to the formation of second messengers that synergistically activate protein kinase C (PKC). The aim of this study was to obtain more insight into the role of PKC in Fc gamma R-mediated killing process. PKC inhibitors H-7 and staurosporine markedly suppressed the killing of S. aureus by monocytes stimulated by cross-linking Fc gamma RI or -II. Cross-linking Fc gamma R caused a transient increase in PKC activity in the membranes of monocytes, as measured by Ca2+/phospholipid-dependent phosphorylation of histone. Western blot analysis revealed that cross-linking Fc gamma R stimulated a transient increase in PKC-beta in the membranes of monocytes with kinetics that correlated closely with the translocation of PKC activity. Cross-linking Fc gamma R on monocytes also stimulated the translocation of PKC-epsilon but not PKC-alpha. PMA and 1-oleoyl-2-acetylglycerol (OAG), which caused translocation of PKC-alpha, -beta, and -epsilon, did not stimulate the killing process. Incubation with these PKC activators for 10 min rendered monocytes unresponsive to stimulation of killing of S. aureus via Fc gamma R. It could be that activation of certain PKC isozymes, probably PKC-alpha and -epsilon, by these activators causes feedback inhibition of PLC and, consequently, the killing in monocytes, because PMA blocks the Fc gamma R-mediated intracellular inositol(1,4,5)P3 formation and PKC translocation. Together, our results indicate that PKC isozymes play an important role in both stimulation and inhibition of the Fc gamma R-mediated intracellular killing of bacteria by monocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Abortive and subclinical poliomyelitis in a family during the 1992 epidemic in The Netherlands.

We describe a case of abortive poliomyelitis due to poliovirus type 3 (PV3) in an unvaccinated woman and a subclinical poliovirus infection in her family during an epidemic in the Netherlands. The woman excreted the epidemic strain (PV3) for 7 weeks. Her two children received oral attenuated poliovirus vaccine and were subsequently found to excrete PV1 and PV2 vaccine strains in addition to the epidemic PV3 strain. Her husband, who had neutralizing antibodies to all three poliovirus types because of previous vaccination, initially excreted no virus; subsequently, however, the vaccine strain PV1 and the epidemic strain PV3 could be cultured from his feces. These observations demonstrate the ease with which poliovirus circulates among family members, including those with neutralizing antibodies.

Adult↗
PubMed1995

High levels of interleukin 10 and tumor necrosis factor alpha in cerebrospinal fluid during the onset of bacterial meningitis.

Since interleukin-10 (IL-10) controls the production of tumor necrosis factor alpha (TNF-alpha) and this latter cytokine has a deleterious effect on neuronal cells, we determined the levels of both cytokines in cerebrospinal fluid (CSF) from children with bacterial meningitis. High levels of IL-10 (1,164 pg/mL) and TNF-alpha (3,158 pg/mL) were detected in CSF from 10 children with meningitis, but these cytokines were not detectable in CSF from 12 controls. In vitro neutralization of IL-10 demonstrated that endogenously formed IL-10 is important for limiting the production of TNF-alpha by leukocytes. We assume that IL-10 in CSF will decrease the inflammatory reaction associated with meningitis and will result in the development of fewer sequelae because of its inhibitory effect on the production of TNF-alpha.

Child↗