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M Röllinghoff

Publications and source records attributed to M Röllinghoff.

At least 127 records · Page 7Linked to original sources
PubMed1990

Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes.

We have previously shown that during an infection with Leishmania major, susceptible BALB/c mice, as opposed to mice of a resistant strain (C57BL/6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor-alpha (TNF-alpha) which is known to be a potent macrophage (M phi) stimulator in other parasitic diseases. In the present study we investigated whether TNF-alpha activates M phi for killing of L. major parasites. In the absence of interferon-gamma (IFN-gamma) or lipopolysaccharide, TNF-alpha (0.025-25,000 U/ml) failed to activate peritoneal exudate M phi from BALB/c mice for killing of L. major amastigotes. In the presence of suboptimal doses of IFN-gamma (5 or 10 U/ml), however, TNF-alpha mediated a rapid elimination of intracellular parasites, which was highly significant compared to IFN-gamma alone. The combination of TNF with interleukin 4, in contrast, was inactive in this respect and allowed survival of intracellular parasites. From these data we conclude that the presence of IFN-gamma is crucial for TNF-alpha-mediated killing of L. major parasites by M phi. Disease progression in susceptible mice therefore seems to be a consequence of a deficiency of IFN-gamma and a predominance of interleukin 4 rather than the result of an excess amount of TNF-alpha.

Animals↗
PubMed1990

Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease-promoting CD4+ cells are different from TH2 cells.

A limiting dilution system has been used for quantitative analysis of antigen-reactive T cells producing interleukin (IL)2, IL4 and interferon (IFN)-gamma in the course of murine infection with Leishmania major. The precursor frequencies of CD4+ cells with the potential for production of IFN-gamma, which has been associated with TH1 cells, are much higher in resistant than in susceptible mice, whereas the reverse is found for CD4+ cells secreting IL4 which have been classified as TH2 cells. Our results allow a better understanding of the relative contribution of these cell types at various stages of disease and can be summarized as follows: (a) secretion of IL4 can be demonstrated in short-term clonal cultures of CD4+ cells from L. major-infected mice, (b) CD4+ cells releasing IL2, suggested to be a characteristic of TH1 cells that predominate in resistant mice, can also be detected in susceptible mice at any time of infection, (c) both IL2 and IL4 are released by the progeny of individual T cells from susceptible mice and (d) the kinetics of precursor frequencies in genetically susceptible mice protected against the disease by prophylactic treatment are different from those of congenitally resistant mice, thus indicating that the development of lymphokine-producing T cells and the establishment of protective immunity may be regulated differently in those mice. The data suggest that resistance to disease is correlated with the presence of IFN-gamma-producing TH1 cells, while susceptibility is associated with CD4+ cells that do not segregate into the TH1 or TH2 subset but display an overlapping pattern of lymphokine activities.

Animals↗
PubMed1990

Immunization of susceptible hosts with a soluble antigen fraction from Leishmania major leads to aggravation of murine leishmaniasis mediated by CD4+ T cells.

This study was performed in order to define Leishmania major antigens that function as disease-modulating immunogens in susceptible BALB/c mice. A soluble leishmanial antigen preparation (S-SLA) derived from highly infective stationary-phase L. major parasites was fractionated by preparative gel electrophoresis. In vitro, the low molecular mass fraction (less than 31 kDa) of S-SLA fraction D (FR D) was found to be a potent stimulator of L. major-specific Th1 and Th2 helper cell clones. In vivo, immunization with FR D induced a Th2-biased immune response in BALB/c mice as determined by the numbers of splenic CD4+ cells secreting interleukin 4 and interferon-gamma according to limiting dilution analyses. In addition, FR D caused significant disease exacerbation in parasite-infected susceptible mice as assessed by the local lesion development and the numbers of parasites in lymph nodes and spleen. This effect was observed after local subcutaneous application of FR D as well as after systemic immunization (intrasplenic or intraperitoneal). Transfer experiments revealed, that the disease-aggravating effect of FR D was mediated by CD4+ T cells. From these results it is concluded that leishmanial protein preparations exist that not only fail to induce protective anitparasitic immunity, but can mediate disease exacerbation, independently of the primary application site of the immunogen. The existence of such structures may serve the parasite as a means to evade the host's immune attack and may also have implications for the development of vaccines.

Animals↗
PubMed1990

Evasion strategies of Leishmania parasites.

Leishmania have long been known to clinicians and parasitologists as the causative agents of a variety of acute or chronic, cutaneous or visceral diseases in mammalian hosts. More recently, these protozoan parasites have evoked the interest of immunologists, as Leishmania infections are an excellent model for studying T-cell dominated antiparasite immune responses. In this review, Christian Bogdan, Martin Röllinghoff and Werner Solbach discuss the multiple interactions of Leishmania with components of the host immune system that illustrate the variety of highly elaborate evasion strategies developed by this parasite.

Journal Article↗
PubMed1990

[Bacterial pathogen and resistance spectrum of the non-irritated conjunctiva. 7,845 preoperative smears at the ophthalmologic clinic of the Erlangen university].

The type and extent of bacterial colonization of the conjunctiva at the time of an intraocular operation may have a major influence on the risk of post-operative endophthalmitis. Between March 1986 and December 1988 a total of 7845 preoperative conjunctival smears were therefore examined by culture of Erlangen University Eye Hospital, in cooperation with the Department of Clinical Microbiology. Altogether, 1221 (15.6%) of the smears were classified as positive. Surgery on the patients concerned was postponed and gentamicin eye drops were administered for decontamination of their conjunctivae until the smears were negative. From the positive smears 1393 strains were cultured, identified, and submitted to a resistance test. The present paper reports the frequency distribution of the species of bacteria isolated and their resistance behavior, and compares the results with those of other authors. The value of preoperative cultures in the prevention of postoperative endophthalmitis and the importance of resistance tests in the context of topical application of antibiotics are discussed.

Bacteria↗
PubMed1990

Production of tumour necrosis factor during murine cutaneous leishmaniasis.

We have assessed the role of tumour necrosis factor-alpha (TNF) during cutaneous leishmaniasis and demonstrated that significant levels of TNF were released by spleen cells from infected mice after in vitro restimulation with Leishmania major promastigotes. Spleen cells from both genetically resistant and genetically susceptible mice were equally capable of producing TNF. After challenge with bacterial endotoxin, TNF activity could also be demonstrated in the serum of L. major-infected mice and the titres correlated with the course of cutaneous disease in susceptible and resistant mice. TNF did not exert a direct leishmanicidal effect in vitro. Furthermore, our study indicated that macrophages are the source of L. major-induced TNF activity and that its elicitation is dependent on the presence of T cells. These findings suggest that TNF acts in concert with other cytokines produced during L. major infection and that its role depends on the composition of T cell subsets and cytokines present.

Animals↗
PubMed1990

Differentiation of serological responses to Yersinia enterocolitica serotype O9 and Brucella species by immunoblot or enzyme-linked immunosorbent assay using whole bacteria and Yersinia outer membrane proteins.

Serum samples from 134 patients showing by the microagglutination test serological cross-reactivity between Yersinia enterocolitica serotype O9 and Brucella spp. were analyzed by immunoblot and enzyme-linked immunosorbent assay techniques for the presence of antibodies directed against plasmid-encoded, yersinia-associated outer membrane proteins (OMPs). Since these OMPs are exclusively expressed in pathogenic strains of Yersinia spp., this characteristic was chosen for serological differentiation of infections caused by these bacteria. The presence of antibodies against plasmid-encoded OMPs of pathogenic Yersinia spp. in patient sera appeared to be a suitable means to identify acute or recent infection with Y. enterocolitica serotype O9, whereas the failure to detect such antibodies indicated an acute or recent infection with Brucella spp.

Antibodies, Bacterial↗
PubMed1989

Studies on the mechanism of polyclonal B cell stimulation by TH2 cells.

Recently, it has been shown that cloned L1/1 T helper cells of type 2 (TH2-cells), when stimulated with antigen, are able to induce polyclonal B cell proliferation. Here we present evidence that this process is dependent on direct cell-cell interaction between T and B cells, which in the effector phase, i.e., during stimulation of the B cells by activated T cells, can be mediated by a mechanism other than cognate interaction. This conclusion is derived from experiments in which highly purified, small B cells of high density were polyclonally stimulated by L1/1 T cells triggered by an anti-T3 monoclonal antibody in the absence of antigen. The triggering process was independent of the presence of the Fc part of the antibody and occurred in cultures devoid of macrophages. Thus, the well-established cognate recognition does not appear to be the only mechanism of B cell induction by T helper cells.

Animals↗
PubMed1989

Suppressive effect of interferon-gamma on the BCL1 cell-dependent interleukin 5 bioassay.

Proliferation of BCL1 cells, generally used for the measurement of murine interleukin (IL)5, is shown to be strongly suppressed by interferon (IFN)-gamma. This effect can be abrogated by the addition of anti-IFN-gamma antibodies. Thus, the IL5 activity of culture supernatants derived from T cells simultaneously producing IFN-gamma and IL5, can only be seen with BCL1 cells in the presence of anti-IFN-gamma antibodies. If anti-IFN-gamma antibodies are omitted, T cells which produce both, IFN-gamma and IL5, may mistakenly be grouped into the TH1 subtype producing only IFN-gamma, but no IL5.

Animals↗
PubMed1989

Detection of cross-reacting epitopes on plasmid-encoded outer membrane proteins of enteropathogenic Yersinia by monoclonal antibodies.

Plasmid-positive Yersinia bacteria of different species and different serotypes were analysed with respect to the immunological relationship of two of their plasmid-encoded outer membrane proteins (OMPs) by the immunoblot technique using three monoclonal antibodies (mAb), which were induced against OMPs of Yersinia enterocolitica serotype O:9 bacteria. Evidence is presented that these OMPs display discrete epitopes, which are common to all plasmid-positive Yersinia strains tested, with only one exception, indicating a close structural relationship of the OMPs analysed.

Antibodies, Monoclonal↗
PubMed1989

Coexistence of antigen-specific TH1 and TH2 cells in genetically susceptible BALB/c mice infected with Leishmania major.

CD4-positive T cell clones with specificity for the protozoan parasite Leishmania major (L. major) of both the protective TH1 and the disease-exacerbating TH2 subtype were isolated from a diseased L. major-infected mouse of the susceptible BALB/c strain. In addition, TH2 cells were isolated from the lesion-draining lymph nodes of an animal clinically healed nine months after sublethal irradiation and subsequent infection. Our data support the notion that the differential outcome of the disease in non-irradiated versus irradiated BALB/c mice reflects the regulation of the two CD4+ T cell subsets. These data also argue against the possibilities that: 1) TH2 cells and their precursors are totally eliminated by irradiation and that 2) TH2 cells are capable of completely hindering the expansion of TH1 cells in diseased animals.

Animals↗
PubMed1989

Proteolysis of the native murine IL 1 beta precursor is required to generate IL 1 beta bioactivity.

We utilized antisera specific for murine IL 1 alpha and IL 1 beta proteins to characterize cell-associated IL 1 according to two distinct criteria, immunochemical detection of radiolabeled IL 1 polypeptides and inhibition of IL 1 activity in cell lysates. Evidence is presented that IL 1 alpha and IL 1 beta are each synthesized by LPS-stimulated but not by unstimulated murine macrophages and accumulate within the cell as intracellular precursors in sizes of 33 kDa and 37 kDa, respectively. As judged by the respective rates of synthesis, IL 1 alpha was about 4-fold more abundant than IL 1 beta. Most (greater than or equal to 95%) of the cell-associated IL 1 activity was inhibited in the presence of the antiserum to IL 1 alpha, suggesting that the precursor of IL 1 beta is mostly biologically inactive. Incubation of cell lysates with papain but not with trypsin or plasmin markedly stimulates an increase in the level of cell-associated IL 1 beta activity and leads to the cleavage of 15-16 kDa carboxyl-terminal fragments from the IL 1 beta precursor. Together, these data indicate that proteolysis of the IL 1 beta precursor is required to generate bioactive IL 1 beta molecules and provide a basis for further investigations of the specific role of proteinases in processing the IL 1 beta precursor to a bioactive form.

Animals↗
PubMed1989

[Parasitic evasion mechanisms: Leishmania as an example].

Leishmania display a variety of mechanisms for effective evasion of the humoral and cellular immune responses of the host which are strongly associated with the expression of two major surface glycoconjugates, gp63 and lipophosphoglycan. The parasites are poor activators of the alternative complement pathway thus avoiding their own extracellular lysis. Complement bound on the surface of promastigotes promotes the uptake of leishmania by macrophages which function as "safe targets" as long as they are not activated by T lymphocytes. This is due to the fact that intracellular parasites are able to 1. decrease the oxidative burst; 2. scavenge toxic oxygen metabolites; 3. inhibit degradative lysosomal enzymes; 4. exploit the acidic milieu of lysosomes for their own metabolism. Finally, leishmania have been shown to evade the host's cellular immune response by down-regulating T cell-activating processes and by initiating the expansion of T cell subpopulations which promote their own survival.

Animals↗
PubMed1989

Cyclosporin A enhances elimination of intracellular L. major parasites by murine macrophages.

In this study we analyzed the influence of cyclosporin A (CyA) on the process of phagocytosis of L. major promastigotes and amastigotes by inflammatory peritoneal macrophages (MP) from BALB/c mice. Our data clearly demonstrate that CyA profoundly enhanced the degradation by peritoneal MP of both intracellular L. major promastigotes and amastigotes. This effect was T cell-independent and specifically associated with CyA, since the similarly structured cyclosporin F (CyF) was ineffective. CyA did not alter the replication and infectivity of extracellular parasites. From these results we conclude that the inhibition of intracellular parasite replication in the presence of CyA substantially contributes to the previously described suppressive effect of CyA on the development of L. major-induced lesions in BALB/c mice.

Animals↗
PubMed1989

Reduction of murine interleukin-1 beta: a possible mechanism in the functional maturation of IL-1 beta.

Studies related to the functional activity of human endogenous pyrogen have emphasized its susceptibility to oxidative inactivation. Here we show that the specific activity of murine IL-1 beta polypeptides can be increased by reduction and subsequent alkylation. This treatment induces a change in the relative molecular weight from 20 kDa to 21 kDa of the molecule, suggesting that conformational changes may play a critical role in the functional maturation of IL-1 beta molecules.

Animals↗
PubMed1988

Application of recombinant granulocyte-macrophage colony-stimulating factor has a detrimental effect in experimental murine leishmaniasis.

The purpose of this study was to evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on BALB/c mice infected s.c. with the intracellular pathogen Leishmania major. Daily i.p. application of 1 microgram rGM-CSF for 21 days following the infection led to an aggravated course of the disease in most animals. In no case was a therapeutic effect observed. In vitro analysis revealed that the parasite burden was approx. 2- to 7-fold higher in the infected lesions, in the lymph nodes draining the infection and in the spleens of rGM-CSF-treated animals than in tissues from nontreated mice. L. major-infected macrophages obtained from chronically infected mice proliferated in the presence of rGM-CSF in vitro without gaining antiparasitic effector function. However, antiparasitic effector function increased and macrophage growth was inhibited in the presence of recombinant interferon-gamma (IFN-gamma). These data indicate that rGM-CSF-induced macrophage proliferation alone is not sufficient to overcome infections with intracellular pathogens like L. major, since simultaneous activation of macrophages by IFN-gamma is required.

Animals↗