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Biomedical subjects

P Smets

Publications and source records attributed to P Smets.

At least 109 records · Page 6Linked to original sources

Immunological activities of RU-41740, a glycoproteic extract from Klebsiella pneumoniae. I.--Activation of murine B cells and induction of interleukin-1 production by macrophages.

RU-41740, a glycoprotein extract from Klebsiella pneumoniae K2O1 strain, is an immunomodulating compound which has been shown to reduce infectious episodes in immunodeficient patients. Data from preliminary experimental designs suggested that RU-41740 could affect several target cells, such as T cells, B cells and macrophages. In the present report, we show that RU-41740 is a selective B-lymphocyte activator. It induces blast transformation in Nude mouse spleen cell cultures and in B-cell-enriched fractions obtained from normal mice. It does not activate T lymphocytes to proliferate. Activation of mouse B lymphocytes by RU-41740 is not affected by removal of adherent cells. RU-41740 also activates immunoglobulin secretion by murine B lymphocytes. Incubating spleen cells from C3H/HeJ mice with RU-41740 results in cell proliferation and activation of antibody-forming cells. This suggests that B-cell activation is not due to LPS contamination. Other experiments show that RU-41740 can also trigger mouse macrophages to produce interleukin-1 activity. Indeed, supernatants from peritoneal adherent cells incubated in the presence of RU-41740 can stimulate blastogenesis in thymocytes from C3H/HeJ mice. Thus, B-cell activation and IL-1 production by macrophages could constitute two additive mechanisms involved in immunomodulation induced by RU-41740.

Animals↗

RU-41740 (K. pneumoniae glycoprotein) enhances resistance to experimental candidiasis and stimulates phagocytic functions.

RU-41740, a purified glycoprotein extract from Klebsiella pneumoniae, (which is an efficient non-specific immune activator in a broad spectrum of in vitro and in vivo reactions) was administered either orally or parenterally in the mouse. It enhanced the resistance of mice to candidiasis, both in terms of survival rate and a decrease in viable yeast cell recovery in kidneys. The drug administered at 0.1 mg or 1 mg/kg augmented 4-fold the mean survival time (MST) of animals infected with 1 to 2 X 10(6) Candida albicans, both by the intraperitoneal and the intravenous route. The effect of the orally administered drug was less striking but nonetheless present. At 10 mg/kg, the MST of infected animals increased about 2-fold. In vitro, in the presence or absence of zymosan, the drug at 10 or 100 micrograms/ml was able to stimulate the phagocytic process of elicited mouse peritoneal cells (65% polymorphonuclear cells, 35% macrophages) and human peripheral blood cells (95% polymorphonuclear cells, 5% monocytes) in terms of activated oxygen species production. The involvement of polymorphonuclear cells in the mechanisms of natural resistance to C. albicans infection led us to discuss the role of these cells as targets for the drug.

Animals↗

Immunological activities of RU-41740, a glycoproteic extract from Klebsiella pneumoniae. II.--Activation of macrophage cytotoxicity against tumour cells and production of a cytotoxic factor.

RU-41740, a glycoprotein extract from Klebsiella pneumoniae, is an immunomodulating agent with a broad spectrum of activities. It enhances several macrophage functions, including interleukin-1 (IL-1) secretion. Present data show that RU-41740 was able to promote murine macrophage cytotoxicity against tumour cells. A soluble cytotoxic factor (CF) was found in supernatants from macrophage cultures stimulated with RU-41740. These supernatants were shown to contain IL-1. CF was detected on L-929 cells sensitized by actinomycin D. CF was analysed on the basis of MW and pHi: after gel filtration on "Ultrogel Aca54", a single peak of CF was found in the range of 50-60 Kd and was then distinct from IL-1, which was eluted at 15 Kd. After chromatofocusing, CF was found in a narrow peak of pH 4.8. CF was detected in supernatants 2 h after macrophage stimulation by RU-41740, and its release was abolished by pretreatment of macrophages with cycloheximide (2 micrograms/ml). CF described here shares several properties with tumour necrosis factor (TNF).

Animals↗

Effect of a long term cholinergic therapy on the gastric acid secretion and on the calculated acid concentration of the parietal component in hypochlorhydric patients.

Fourteen hypochlorhydric patients suffering from atrophic gastritis were tested with pentagastrin and randomly distributed in groups treated per os : one by a placebo, the other by eserine amine oxide. In the placebo group we did not observe a variation in the acid output nor in the acid concentration of the parietal component. In the patients treated with eserine amine oxide, the acid secretion and the acid concentration of the parietal component increased on treatment (p less than 0.01). In two other groups of hypochlorhydric patients tested with pentagastrin (n = 25) or with histamine ( n = 38) and treated for periods of one to three months we also observed an increase in the acid output and the acid concentration of the parietal component. These facts could be explained by an increase in the number of functional cell units, accompanied by a qualitative variation in the parietal component during treatment the patients suffering from atrophic gastritis.

Achlorhydria↗