H.L. Ko

Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and d-galactose

SummaryAccording to our hypothesis, organ-specific lectins (e.g., the d-galactose-specific hepatic binding protein) play an important role in the organ location of metastatic malignant cells. The rapid clearance and uptake by the liver of tritiated α-acid-(asialo)glycoprotein from the circulation of Balb/c mice was markedly delayed after preinjection of d-galactose or arabinogalactan. The preinjection (1h) and regular application (for 3 days after tumor cell inoculation in Balb/c mice) of the receptor blocking agents d-galactose and arabinogalactan prevented the settling of sarcoma L-1 tumor in the liver completely, but did not influence the settling in the lung. Other galactans, dextrans, and phosphate-buffered saline showed no effect. Therefore, when lectins were blocked with competitive-specific glycoconjugates, colonization was prevented.

Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan.

Repeated administration of the hepatic lectin blocking agents D-galactose or arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/c mice and greatly reduced the colonization process of highly metastatic ESb lymphoma cells of the liver of DBA/2 mice. Therefore, when hepatic lectins were blocked with competitive glycoconjugates, tumor cell colonization of the liver could be prevented in two different model systems.

Digestive tract microflora liberates low molecular weight peptides with immunotriggering activity

Antibiotic digestive tract decontamination in BALB/c-mice resulted in a significant reduction of peritoneal macrophage function and lymphocyte proliferation. Considerable evidence has accumulated showing that certain species of the indigenous gastrointestinal (GI)-tract microflora, e.g. Bacteroides sp., Clostridium sp., Lactobacillus sp., and Propionibacterium sp., liberate low molecular weight peptides which are able to trigger basic immune responses. Eradication of the GI-tract microflora apparently results in a lack of peptide production correlating to immunosuppression in experimental BALB/c-mice. Substitution of peptides in GI-tract decontaminated mice reconstituted macrophage function as well as proliferation of lymphatic tissue.

In vitro and in vivo inhibition of lectin mediated adhesion of pseudomonas aeruginosa by receptor blocking carbohydrates

SummaryIn vitro andin vivo experiments with Balb/c mice andPseudomonas aeruginosa ATCC 27853 supported our hypothesis that bacterial lectins play an important role in the organotropy of infectious diseases.In vitro andin vivo adhesion ofP. aeruginosa was mediated by N-acetylneuraminic acid (NANA) receptors. Blocking of the binding sites (lectins) on the bacterial surfaces with competitive specific carbohydrates (NANA) completely prevented the bacterial adhesion processin vitro.In vivo the number of adherent organisms in various organs decreased dramatically in the presence of NANA, whereas non-related carbohydrates (e.g. D-galactose) just showed negligible effects. Additionally, the application of NANA-treated organisms protected the animals from septicemia and death. Therefore, blocking of bacterial lectin receptors with specific carbohydrates might be of clinical relevance to prevent bacterial attachment to organ cells.ZusammenfassungExperimentelleIn vitro- undIn vivo-Studien mit Balb/c-Mäusen und demPseudomonas aeruginosa-Stamm ATCC 27853 bestätigten unsere Hypothese, daß bakterielle Lektine für die Organotropie von bakteriellen Infektionskrankheiten von besonderer Bedeutung sind. Die Adhäsion vonP. aeruginosa an Parenchymzellen verschiedener Organe (Lunge, Leber, Niere) wurdein vitro undin vivo durch N-Acetylneuraminsäure-(NANA-)spezifische bakterielle Rezeptoren (Lektine) vermittelt. Blockade der Bakterienlektine mit Rezeptor-komplementären Kohlenhydraten (NANA) verhinderte die Adhäsion vonP. aeruginosa in vitro.In vivo bewirkten NANA-Injektionen eine drastische Reduktion der adhärierenden Keime in Lunge, Leber und Niere, während andere Kohlenhydrate (z. B. D-Galaktose) keine Auswirkungen auf den Organbefall zeigten. Folgerichtig könnten sich aus diesen Befunden therapeutische Aspekte ergeben, da eine Lektinblockade mit spezifischen Glykokonjugaten bakterielle Organbesiedlungen verhindern könnte.

Immunomodulation by Propionibacteria

Summary The ability of bacteria and bacterial products to modulate the immune response to unrelated antigens is well documented. Propionibacteria are amongst the most potent immunomodulators stimulating cell populations involved in nonspecific resistance. Generally, the activated immune system provides protection from infectious pathogens and malignancies via mechanisms of recognition and elimination. Accordingly, administration of propionibacteria could be shown to be of benefit in the treatment of neoplastic and infectious diseases. Thus, it can be recommended for further clinical investigations.

Glycoprotein modifications of sarcoma L-1 tumor cells by tunicamycin, swainsonine, bromoconduritol or 1-desoxynojirimycin treatment inhibits their metastatic lung colonization in Balb/c-mice

SummarySynthesis and expression of cell surface carbohydrates appear to be involved in recognition events associated with tumor invasion and metastasis. Thus, the potential of murine sarcoma L-1 cells to form experimental lung metastases after i.v. injection was assessed after inhibiting tumor cell protein glycosylation with tunicamycin, swainsonine, bromoconduritol, or 1-desoxynojirimycin. Incubation of sarcoma L-1 cells with 0.5 μg (or above) of these substances/ml medium for 20–24 h significantly inhibited lung colonization. Cytotoxic side effects or additional organ manifestations could not be found. Gas liquid chromatographic examinations of carbohydrates from treated L-1 cells indicated that sugar synthesis was evidently inhibited. These results suggest that specific glycan structures on tumor cells are required for expression of the metastatic phenotype.

Blocking of lectin-like adhesion molecules on pulmonary cells inhibits lung sarcoma L-1 colonization in BALB/c-mice.

Adhesion and inhibition experiments with pulmonary cells of BALB/c-mouse origin and syngeneic sarcoma L-1 cells indicated that L-fucose specific lectin-like adhesion molecules, presumably situated on pulmonary cell surfaces are (at least partly) responsible for the specificity of this cell-cell interaction. Addition of specific sugars and glycoconjugates (L-fucose and fucoidan, respectively) to the incubation medium evidently inhibited the adhesion process as quantified using radiolabelled tumor cells. Unspecific carbohydrates (e.g. D-galactose) did not affect the cellular interaction. In vivo, repeated administration of fucoidan (but not of unspecific glycoconjugates) significantly inhibited the settling of metastatic sarcoma L-1 cells in the lungs of BALB/c-mice. Therefore, when lectin-like adhesion molecules on pulmonary cells were blocked with competitive glycoconjugates, tumor cell colonization of the lung could be significantly inhibited.

Stimulation of human monocyte chemiluminescence by staphylococcal lipoteichoic acid.

Lipoteichoic acid (LTA) from Staphylococcus saprophyticus strains S1 and S35 was shown to be a potent stimulator of human monocyte chemiluminescence, whereas human granulocytes were not activated. Data on the chemical analysis of these LTA-preparations were given.

Comparative study on the immunostimulatory potency of differentPropionibacterium strains

Abstract198 strains ofPropionibacterium acnes, P. avidum, andP. granulosum were tested for their immunostimulatory potency using splenomegaly as index of stimulation, the activity differed widely from strain to strain. The antitumor and antimetastatic properties of six strains with differing stimulation activities were carefully examined. A close correlation between spleen enlargement and antitumor effects could be observed. The simple spleen enlargement test is recommended for determination of the immunopotency of propionibacteria and for the standardisation of vaccine preparations.

Lectin-Mediated bacterial adhesion to human tissue

In vitro experiments with frozen sections of human lung and kidney demonstrated that adhesion ofStreptococcus pneumoniaePn 629 Type 14 andPseudomonas aeruginosaATCC 27853 to human cells was mediated by bacterial lectins (adhesins) with N-acetyl-D-glucosamine/D-galactose or N-acetyl-neuraminic acid specificity. Blocking of the lectin binding sites on bacterial surfaces with competitive carbohydrates completely prevented the bacterial adherence,whereas non-specific carbohydrates (D-mannose, D-xylose) did not inhibit adherence.