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R Lelchuk

Publications and source records attributed to R Lelchuk.

At least 37 records · Page 2Linked to original sources
PubMed1985

Serum IL-2 inhibitor in mice. II. Molecular characteristics.

The molecular characteristics of a serum IL-2 inhibitor were determined by fractionating active sera from normal and malaria-infected mice, and assaying inhibitory activity in blocking production and expression of IL-2 activity. Using isoelectric focusing and ion exchange chromatography, the activity resolved in a single peak (pI = 6.2). HPLC gel filtration resolved two peaks of activity (50,000 and 25,000 MW) which are probably related. The molecule is precipitated by 50% saturated ammonium sulphate, and is destroyed by heating above 56 degrees or by acidification below pH 4.

Animals↗
PubMed1985

Macrophage functions in Biozzi mice.

The faster degradation of antigen by macrophages in Biozzi low (L) responder mice, compared to Biozzi high (H) responder mice, is thought to be responsible for their lower antibody response. We have measured four functions associated with macrophages to see whether macrophages from L mice were generally more active than those from H mice. Peritoneal macrophages obtained from normal mice were compared with those from groups of mice given Mycobacterium bovis BCG or Propionibacterium acnes. Cells from normal H mice gave a stronger oxidative burst when triggered with phorbol myristate acetate, and were more cytotoxic for tumour cells than cells from L mice. Cells from all mice injected with BCG or P. acnes gave a stronger oxidative burst, and were more cytotoxic for tumour cells; again, both responses were higher in H mice than in L mice. By contrast, when groups of mice that had received P. acnes were given endotoxin and bled, higher titres of tumour necrosis factor were found in the sera of L mice. Spleen cells from both lines of mice released similar levels of interleukin-1, both spontaneously and in response to lipopolysaccharide. Our results suggest that these various macrophage responses are expressed independently in H and L mice.

Animals↗
PubMed1985

Serum IL-2 inhibitor in mice. I. Increase during infection.

Serum from normal mice contains an inhibitor of interleukin-2 (IL-2) which probably interacts directly with IL-2. Athymic mice and normal mice kept under specific pathogen-free conditions do not show this activity, whereas mice infected with malaria parasites have increased serum levels of inhibitor. This IL-2 inhibitor may play an important part in regulating T-cell function.

Animals↗
PubMed1984

Changes in the capacity of macrophages and T cells to produce interleukins during murine malaria infection.

Interleukin 1 (I1-1) produced by activated macrophages and interleukin 2 (I1-2) released by a subset of T lymphocytes upon antigen or mitogen stimulation are the soluble mediators involved in the mechanism of T-cell activation, proliferation, and differentiation. Since these T-cell responses are depressed during malaria infection, the capacity of macrophages to produce I1-1 following lipopolysaccharide (LPS) stimulation and that of lymphocytes to release I1-2 upon stimulation with concanavalin A (Con-A) in mice infected with either nonlethal Plasmodium yoelii (NLPY) or lethal Plasmodium berghei (PB) malaria parasites was analyzed. The results show that while adherent cells from spleen or peritoneal exudates of infected mice were able to produce I1-1, although to a different extent in the two infections, splenic lymphocytes were unable to produce I1-2, but capable of responding to it. This suggests that the diminished T-cell responses in malaria might be due to a defect of I1-2 synthesis.

Animals↗
PubMed1983

The differential effect of 2-deoxyguanosine on concanavalin A-induced suppressor and cytotoxic activity.

The effect of 2-deoxyguanosine (dGuo) on the generation in vitro of nonspecific suppressor cells in murine spleen cell cultures by concanavalin A (Con A) is examined. The experiments indicate that dGuo abrogates the generation of nonspecific suppressor activity by lectin stimulation of murine spleen cells. When comparisons were made between the effect of this nucleoside on the generation of suppressor and cytotoxic cells by Con A stimulation of murine spleen cells, it was found that dGuo only affected the generation of suppressor cells. The development of lectin-stimulated cytotoxicity was not affected by dGuo. In addition it was found that dGuo does not affect the NK activity of murine spleens.

Animals↗
PubMed1983

T-independent macrophage changes in murine malaria.

A study to investigate the participation of T cells in macrophage-mediated responses during malaria was performed in nude (nu/nu) and littermate (nu/+) mice infected with Plasmodium berghei (PB). We found that in both groups of mice spleen cells suppressed the mitogenic response to LPS. Both nu/+ and nu/nu infected mice also showed liver macrophage activation, reflected by increased plasminogen activator release. These findings suggest that at least some of the macrophage changes during malaria infection are T-independent.

Animals↗
PubMed1981

Differential involvement of non-specific suppressor T cells in two lethal murine malaria infections.

The suppression of the contact sensitivity of oxazolone in murine malaria is shown to be mediated by non-specific T suppressor cells, but to a different extent in infection caused by two different species of parasite. Depletion of T suppressor cells in vivo and/or anti-Thy 1.2 treatment in vitro indicated that in mice infected with P. berghei the suppressor effect was largely mediated by T cells. By contrast, in mice infected with a lethal strain of P. yoelii it was only partly due to T cells; B suppressor cells and/or macrophages may also be involved. However, depletion of T suppressor cells in vivo had no effect on the course of the parasitaemia or on the survival time. Therefore, we postulate that this kind of non-specific immunosuppression cannot be regarded as a major cause of lethality.

Animals↗
PubMed1980

Two distinct types of non-specific immunosuppression in murine malaria.

A comparative study of non-specific immunosuppression by malaria has been carried out in five situations: in both unvaccinated and vaccinated mice infected with the lethal Plasmodium yoelii or the lethal Plasmodium berghei, and in the unvaccinated non-lethal P. yoelii infection. Spleen cells showed a suppressive effect on the normal blastogenic response to mitogens. This suppression was strongest in the mice vaccinated before infection with the lethal P. yoelii and in those infected with non-lethal P. yoelii, suggesting that the suppressive effect did not interfere with recovery. Silica, anti-Thy-1, and indomethacin treatment suggested that this suppression was caused by macrophages. However, the plaque-forming cell response to sheep RBC in vivo was suppressed equally in every case at the peak of the parasitaemia, whereas the suppression of contact sensitivity to oxazolone was strongest in mice with fatal infections. We suggest that different suppressor mechanisms operate in malaria, some being harmful to the host and others possibly beneficial.

Animals↗
PubMed1979

Development and suppression of a population of late-adhering macrophages in mouse malaria.

Changes in phagocytic and adherent cell numbers were compared during the course of infections of mice with Plasmodium yoelii (Py) and P. berghei (Pb) and in vaccinated mice challenged with homologous parasites. Nucleated cells in the spleen increased in number in Py-infected mice and were maximal at the time of recovery. The number of phagocytic cells increased in parallel, as did the number of blood leucocytes. Rates of increase were accelerated in vaccinated mice. Changes in Pb-infected mice resembled controls and blood leucocytes showed no consistent increase. In infected mice, the number of spleen and bone marrow cells which adhered to plastic rose above normal. At some stages of infection, cells which did not adhere in 24 h did so in 72 h. Such late-adhering cells, which resembled macrophages in morphology, were most numerous at the time of recovery. They appeared to be derived from monocyte precursors which matured in culture. Sometimes cells adherent at 24 h suppressed the development of the late-adhering population. Silica invactivated these suppressive macrophages but did not affect the precursors which developed into late-adhering cells. It is concluded that malarial infection stimulates the production of precursors of the macrophage-monocyte series and that their development is regulated by the presence of mature macrophages.

Animals↗
PubMed1977

Cell-mediated immunity in Chagas' disease: Alterations induced by treatment with a trypanocidal drug (nifurtimox).

Peripheral leucocyte migration inhibition (LMI) with Trypanosoma cruzi-specific antigens, measured as a migration index (MI), was studied in chronic Chagas' disease patients. The MI of untreated patients with polymerized antigens from culture forms (epimastigotes) of T. cruzi was significantly lower than that of controls. In contrast, when chronic Chagas' patients were treated with nifurtimox, 10 mg/kg/day for 2 months, the MI was not different from control values. Treated and untreated patients had normal T- and B-lymphocyte markers, measured by the ability to form rosettes either with sheep erythrocytes (E-RFC) or with sheep erythrocytes--antibody--complement (EAC-RFC). In addition, the number of lymphocytes bearing surface membrane Ig (SMIg) was the same as that of controls. Non-specific functional assays, such as PHA-induced blastogenesis and antibody-dependent cell-mediated cytotoxicity (ADCC) to sensitized chicken erythrocytes were also normal, both in treated and untreated patients. Thus, nifurtimox produced a particularly effect on cell-mediated immunity, specially detectable using LMI.

Cell Migration Inhibition↗
PubMed1977

Nifurtimox-induced alterations in the cell-mediated immune response to PPD tin guinea-pigs.

Positive skin reactions to PPD in guinea-pigs immunized with Freund's complete adjuvant (FCA) were reversed after treatment with 10 mg/kg/day nifurtimox for 12 days. The in vitro migration of peripheral blood leucocytes from FCA-immunized guinea-pigs was inhibited with PPD, but it returned to normal values after nifurtimox treatment. Furthermore, the cell-free supernatant from PPD-stimulated lymphocytes from FCA-immunized nifurtimox-treated guinea-pigs did not inhibit the migration of normal cells. Thus the administration of nifurtimox impaired the specific cell-mediated immune response to PPD both in vivo and in vitro.

Animals↗
PubMed1975

The modifications of the final stages of the complement reaction by alkali metal cations.

We studied the effects of alkali metal cations on the terminal stages of complement lysis of human and sheep HK erythrocytes. Sensitized erythrocytes (EA) were reacted with limited amounts of complement for 1 hr at 37 degrees C in buffer containing 147 mM NaCl (Na buffer), which resulted in 10-40% lysis. The unlysed cells were washed with Na buffer at 0-2 degrees C and incubated for 1 hr at 37 degrees C in buffers containing 147 mM of the various alkali metal cations. Although additional lysis (25 to 65%) occurred with K, Rb, or Cs buffer, only minor degrees developed with Na or Li buffer, only minor degrees developed with Na or Li buffer. Intermediate levels occurred with 100 mM of the divalent alkali cations. Halogen ions and SCN-(147 MM), Ca++ (0.15mM), and Mg++ (0.5 mM) did not alter the effect of the alkali metal cations. Lysis occurring in K+, Rb+ or Cs+ proceeded without lag, was temperature dependent with an optimum of 43 degrees C, and had a pH optimum of 6.5. Lysis in K and Na buffers was unaffected by 10(-3) to 10(-5) M ouabain. Experiments with mixtures of cations indicated that Na+ had a mild inhibitory effect that could be totally overcome by K+, partially by Rb+, and not at all by Cs+. Li+ had a strong inhibitory effect, 6 X 10(-5) M causing 50% inhibition in buffers containing 147 mM K+, Rb+, or Cs+. By using intermediate complexes of EA and purified complement components we demonstrated that K+ enhances the lytic action of C8 on EAC1-7 as well as that of C9 on EAC1-8. It was known that Li+ facilitates lysis when acting on the entire complement reaction. We found that Li+ enhanced the lytic action of C8 on EAC1-7, with a kinetic that differed from that of the K+ effect. In addition, Li+ inhibited the enhancing effect of K+ upon lysis of EAC1-8 by C9. This occurred at concentration of Li+ similar to those which inhibited the additional lysis by K+, Rb+, and Cs+ of cells that were pretreated in Na buffer with the entire complement sequence. We propose that the major effects of alkali metal cations on complement lysis are due to their interaction with C8 and/or membrane constitutes.

Adenosine Triphosphate↗
PubMed1972

Role of complement in immune lysis of Trypanosoma cruzi.

Studies were performed on the mechanism of immune lysis of culture forms of Trypanosoma (Schizotrypanum) cruzi. Antibody-mediated lysis is caused by complement, which is activated via the classical pathway. The properdin system is not required. The kinetics of the reaction is similar to that followed by immune lysis of sensitized sheep erythrocytes, as is the concentration of divalent cations required for optimal lysis (0.15 mm Ca(2+) and 0.5 mm Mg(2+)), the occurrence of cell membrane uptake of the complement components C3 and C4, and the development of characteristic ultrastructural modifications on the cell membrane.

Agglutination Tests↗