The in vitro activity of lectin I from mistletoe (ML I) and its isolated A and B chains on functions ofmacrophages and polymorphonuclear cells

Metzner, G; Franz, H.; Kindt, A; Fahlbusch, B; Süß, Jochen

doi:10.1016/s0171-2985(85)80002-4

Cited by 31 publications

(18 citation statements)

References 14 publications

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“…It is, however, doubtful, whether these tests truly reflect the mechanism of action of the mistletoe proteins, since it has been shown that mis tletoe lectin can also stimulate the unspecific immune defence system [8]. Very probably, the highly diluted mistletoe extracts that arc applied parenterally act via immune induction, rather than a direct cytostatic ef fect.…”

Section: Existing Attempts At Standardizationmentioning

confidence: 99%

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Studies on the Standardization of Mistletoe Preparations

Wagner¹,

Jordan²,

Feil³

1986

Oncology

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The newly isolated phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E and the high molecular lectins and viscotoxins were selected for a standardization of mistletoe extracts and drug preparation. The phenylpropanoids found in all alcoholic and aqueous extracts were suitable for an HPLC fingerprint analysis, and for quantitative determination. The lectin content of the drug preparations was determined by single radial immunodiffusion. As shown by the isoelectric focussing method, Iscador® and fermented mistletoe extracts contain only the mistletoe lectins ML II/III, whereas the proteins of the ML I complex are missing. For identification and quantitative determination of viscotoxins, an HPLC method was designed.

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Section: Existing Attempts At Standardizationmentioning

confidence: 99%

“…In view of their cytotoxic [25] and immunomodulatory properties [8], the lectins seem to be the most interest ing of these three groups of constituents.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Standardization of Mistletoe Preparations

Wagner¹,

Jordan²,

Feil³

1986

Oncology

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“…Vor mehr als 12 Jahren wurde entdeckt, dass VAA-I und seine BKette die Phagozytoseaktivita Èt der humanen Leukozyten stimulieren [50]. Wie schon erwa È hnt, zeigen Monozyten und Granulozyten eine gro È ssere Affinita Èt zu VAA-I als Lymphozyten [38].…”

Section: Lektin-induzierteunclassified

Zukunft der Misteltherapie aus pharmakologischer Sicht

1999

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Because of their cytostatic/apoptotic and immunomodulatory effects mistletoe extracts are often applied in tumour patients. Recent experimental data suggest that the mistletoe lectins Viscum album agglutinin (VAA)-I and -II are play an important role in the efficacy of mistletoe therapy. VAA-I and -II are members of the type-II ribosome-inactivating proteins. VAA-I has been shown to induce cytostatic effects in cultures of various eukaryotic cells in vitro. In 24-hour cultures of human peripheral lymphocytes, flow-cytometric investigations with propidium iodide (PI) in hypotonic buffer and quantitative assessment of DNA breaks with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay were carried out; they revealed a dose-dependent VAA-I-induced apoptosis (lectin concentrations between 10 ng/ml and 1 μg/ml). In 24-hour cultures of peripheral blood mononuclear cells (PBMC), VAA-I in non-cytotoxic concentrations (1±10 ng/ml) induced mRNA expression and enhanced the secretion of proinflammatory cytokines. The stimulation of NK cells by VAA-I in vitro was enhanced in additive manner by the combination of VAA-I with IL-2 and IL-12. In culture of PBMC and bone marrow CD34⁺ cells coincubation of VAA-I with other haematopoietic growth factors induced a dose-dependent increase in clonogenic growth. In cancer patients the mechanisms of natural immunity, believed to be essential for their survival, are often significantly decreased. VAA-I and standardized mistletoe extracts are able to stimulate the cellular parameters of natural immunity with a bell-shaped curve of efficacy. Studies in animal models suggest that application of 0.5–3 ng/kg VAA-I twice a week is effective in sustaining the elevation of the number and activity of peripheral blood NK cells. These parameters often exhibit high intrinsic fluctuations, in healthy persons, however, blind crossover studies reveal an optimal lectin dose of about 0.5 and 1 ng/kg bw, suggesting a potential use of mistletoe preparations as a modulator of the natural immune system. Selective apoptotic effects of VAA-I may represent a novel approach for pharmacological manipulation of the balance between cell growth and programmed cell death. Appropriate combination of immunomodulatory and cytotoxic doses may open new clinical perspectives in the mistletoe therapy.

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“…(2) Activation of macrophages: ML I has no cyto toxic effect on human granulocytes and paraffin oilstimulated macrophages from guinea pig between 10" 14 and 1 0 '8 M (trypan blue and cthidium bromide exclusion [34]). Similar results have been reported by Luther et al [30], Over the same concentration range.…”

Section: Further Biological Activities Of the A And B Chains Of Mistlmentioning

confidence: 99%

Mistletoe Lectins and Their A and B Chains

Franz¹

1986

Oncology

126

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Mistletoe lectins are of high biological activity. The mistletoe lectin I (ML I) is a naturally occurring conjugate of an enzyme (A chain) and a lectin (B chain). Its cytotoxicity is caused by inhibiting the protein synthesis on the ribosomal level. Prominent properties of the A chain are mitogenicity and inhibition of the protein synthesis in cell-free systems. The A chain is also a candidate for the construction of immunotoxins. The B chain as well as the intact lectins activate macrophages and release lymphokines from lymphocytes. They both inhibit the allergen-induced histamine release from leukocytes and the collagen-induced serotonin release from platelets. It cannot be excluded that the combination of selectively cytotoxic and immunopotentiating properties of mistletoe lectins and their chains are decisive for the therapeutic effects of mistletoe preparations.

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The in vitro activity of lectin I from mistletoe (ML I) and its isolated A and B chains on functions ofmacrophages and polymorphonuclear cells

Cited by 31 publications

References 14 publications

Studies on the Standardization of Mistletoe Preparations

Studies on the Standardization of Mistletoe Preparations

Zukunft der Misteltherapie aus pharmakologischer Sicht

Mistletoe Lectins and Their A and B Chains

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