RRC ID 18631
Author Ito H, Sagane Y, Miyata K, Inui K, Matsuo T, Horiuchi R, Ikeda T, Suzuki T, Hasegawa K, Kouguchi H, Oguma K, Niwa K, Ohyama T, Watanabe T.
Title HA-33 facilitates transport of the serotype D botulinum toxin across a rat intestinal epithelial cell monolayer.
Journal FEMS Immunol Med Microbiol
Abstract A large size botulinum toxin complex (L-TC) is composed of a single neurotoxin (BoNT), a single nontoxic nonhaemagglutinin (NTNHA) and a haemagglutinin (HA) complex. The HA complex is comprised of three HA-70 molecules and three arm structures of HA-33/HA-17 that consist of two HA-33 and a single HA-17. In addition to the mature L-TC, smaller TCs are present in cultures: M-TC (BoNT/NTNHA), M-TC/HA-70 and immature L-TCs with fewer HA-33/HA-17 arms than mature L-TC. Because L-TC displays higher oral toxicity than pure BoNT, it was presumed that nontoxic proteins are critical for food poisoning. In this study, the absorption of TCs across intestinal epithelial cells was assessed by examining the cell binding and monolayer transport of serotype D toxins in the rat intestinal epithelial cell line IEC-6. All TCs, including pure BoNT, displayed binding and transport, with mature L-TC showing the greatest potency. Inhibition experiments using antibodies revealed that BoNT, HA-70 and HA-33 could be responsible for the binding and transport. The findings here indicate that all TCs can transport across the cell layer via a sialic acid-dependent process. Nonetheless, binding and transport markedly increased with number of HA-33/HA-17 arms in the TC. We therefore conclude that the HA-33/HA-17 arm is not necessarily required for, but facilitates, transport of botulinum toxin complexes.
Volume 61(3)
Pages 323-31
Published 2011-4-1
DOI 10.1111/j.1574-695X.2011.00779.x
PMID 21219447
MeSH Animals Botulinum Toxins / metabolism* Cell Line Epithelial Cells / metabolism* Protein Transport Rats
Times Cited 34
WOS Category INFECTIOUS DISEASES MICROBIOLOGY IMMUNOLOGY
Resource
Human and Animal Cells IEC 6(RCB0993)