Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A{sub 2}-induced degranulation in mast cells
Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of {beta}-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G{sub M1}), di-sialoganglioside (G{sub D1a}) and tri-sialoganglioside (G{sub T1b}). In contrast, honeybee venom-derived phospholipase A{sub 2} induced the net degranulation directly without cytotoxicity, which was not inhibited by G{sub M1}, G{sub D1a} and G{sub T1b}. For analysis of distribution of G{alpha}{sub q} and G{alpha}{sub i} protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of G{alpha}{sub q} and G{alpha}{sub i} at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A{sub 2}-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A{sub 2}-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting.
- OSTI ID:
- 21535286
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 252, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.02.011; PII: S0041-008X(11)00057-3; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ADRENALINE
BEES
CONNECTIVE TISSUE
DOGS
GANGLIOSIDES
MAST CELLS
SACCHAROSE
TOXICITY
TOXINS
VENOMS
ADRENAL HORMONES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIGENS
ARTHROPODS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARBOHYDRATES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CONNECTIVE TISSUE CELLS
DISACCHARIDES
DRUGS
GLYCOLIPIDS
HAZARDOUS MATERIALS
HORMONES
HYMENOPTERA
INSECTS
INVERTEBRATES
LIPIDS
MAMMALS
MATERIALS
NEUROREGULATORS
OLIGOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
SACCHARIDES
SOMATIC CELLS
SYMPATHOMIMETICS
TOXIC MATERIALS
VERTEBRATES