Abstract |
Viscum album agglutinin-I (VAA-I) is a plant lectin which possesses antitumoral properties. This lectin is also known for its immunostimulatory effects when used at low concentrations (1-100 ng/ml). We have demonstrated recently that VAA-I is a potent inducer of human neutrophil apoptosis in vitro when used at higher concentrations. The role of VAA-I on activated neutrophils has not so far been investigated and its potential proinflammatory properties in vivo are poorly documented. Herein, we demonstrated that VAA-I (1000 ng/ml) induces apoptosis in lipopolysaccharide (LPS)-treated human neutrophils in vitro as well as in murine neutrophils isolated from lipopolysaccharide (LPS)-induced neutrophil influx. Using this model, we found that administration of VAA-I (100 or 1000 ng/ml) did not induce an inflammatory response. However, when used at 1 or 10 ng/ml, VAA-I was found to significantly induce a transitory inflammatory response, based on an increased leucocyte infiltration (>98% neutrophils). Also, we found that VAA-I inhibits LPS-induced neutrophil influx when administered simultaneously with LPS. In such conditions, some characteristic apoptotic neutrophils were observed in the pouch. Unlike LPS, which increased the production of some cytokines, VAA-I (1 or 10 ng/ml) did not increase the production of tumour necrosis factor ( TNF)-alpha, interleukin (IL)-1Ra, IL-1alpha, IL-beta, IL-8, IL-10 or IL-12 (p70) in human neutrophils. We conclude that VAA-I possesses the ability to induce apoptosis of preactivated neutrophils at a concentration that does not induce a proinflammatory response. Moreover, we conclude that VAA-I can inhibit a LPS-induced proinflammatory response in vivo. These data may provide new clinical perspectives in future mistletoe therapy and favour its potential utilization based on anti-inflammatory activity that at first appears contradictory with its use as immunostimulant.
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Authors | V Lavastre, H Cavalli, C Ratthe, D Girard |
Journal | Clinical and experimental immunology
(Clin Exp Immunol)
Vol. 137
Issue 2
Pg. 272-8
(Aug 2004)
ISSN: 0009-9104 [Print] England |
PMID | 15270843
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Cytokines
- Lipopolysaccharides
- Plant Preparations
- Plant Proteins
- Ribosome Inactivating Proteins, Type 2
- Toxins, Biological
- VAA-I protein, Viscum album
- ribosome inactivating protein, Viscum
- Ribosome Inactivating Proteins
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Apoptosis
(drug effects)
- Cytokines
(biosynthesis)
- Humans
- Inflammation
(prevention & control)
- Lipopolysaccharides
(pharmacology)
- Mice
- Neutrophil Activation
(drug effects)
- Neutrophils
(drug effects)
- Plant Preparations
(pharmacology)
- Plant Proteins
(pharmacology)
- Ribosome Inactivating Proteins
- Ribosome Inactivating Proteins, Type 2
- Toxins, Biological
(pharmacology)
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