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Effects of botulinum toxin type D on secretion of tumor necrosis factor from human monocytes

Journal Article · · Mol. Cell. Biol.; (United States)
DOI:https://doi.org/10.1128/MCB.9.5.2239· OSTI ID:5822683
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Botulinum toxins are potent neurotoxins which block the release of neurotransmitters. The effects of these toxins on hematopoietic cells, however, are unknown. Monocytes secrete a variety of polypeptide growth factors, including tumor necrosis factor (TNF). In the study reported here, the effects of botulinum toxin type D on the secretion of TNF from human monocytes were examined. The results demonstrate that biotulinum toxin type D inhibits the release of TNF from monocytes activated by lipopolysaccharide (LPS) but not by 12-O-tetradecanoylphorbol-13-acetate. Botulinum toxin type D had no detectable effect on intracellular TNF levels in LPS-treated monocytes, indicating that the effects of this toxin involve the secretory process. This inhibitory effect of botulinum toxin type D on TNF secretion from LPS-treated monocytes was partially reversed by treatment with 12-O-tetradecanoylphorbol-13-acetate or introduction of guanosine 5'-(/gamma/-thio)t-riphosphate into these cells. The results demonstrate that TNF secretion is regulated by at least two distinct guanine nucleotide-binding proteins, one responsible for the activation of phospholiphase C and another which acts as a substrate for botulinum toxin type D. ADP-ribosylation of monocyte membranes by botulinum toxin type D demonstrated the presence of three substrates with M/sub r/s of 45,000, 21,000, and 17,000. While the role of these substrates in exocytosis is unknown, the results suggest that the M/sub r/ 21,000 substrate is involved in a process other than TNF secretion.
Research Organization:
Lab. of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (US)
OSTI ID:
5822683
Journal Information:
Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 9:5; ISSN MCEBD
Country of Publication:
United States
Language:
English

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Related Subjects

550200* -- Biochemistry
551000 -- Physiological Systems
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ANIMALS
ANTIGENS
AUTONOMIC NERVOUS SYSTEM AGENTS
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CARBOXYLESTERASES
CARCINOGENS
CLOSTRIDIUM
CLOSTRIDIUM BOTULINUM
DRUGS
ENDOTOXINS
ENZYME INDUCTION
ENZYMES
ESTERASES
ESTERS
FUNCTIONS
GENE REGULATION
GROWTH FACTORS
GTP-ASES
HYDROLASES
LEUKOCYTES
LIPASE
LIPIDS
LIPOPOLYSACCHARIDES
MAMMALS
MAN
MATERIALS
MICROORGANISMS
MITOGENS
MOLECULAR BIOLOGY
MONOCYTES
NEUROREGULATORS
ORGANIC COMPOUNDS
PHORBOL ESTERS
POLYSACCHARIDES
PRIMATES
PROTEINS
SACCHARIDES
TOXIC MATERIALS
TOXINS
VERTEBRATES