TY - JOUR
T1 - The effect of shiga toxin and sonicates of Shigella isolates from children with neurologic manifestation on neuroblastoma cell lines
AU - Ashkenazi, S.
AU - Yuhas, Y.
AU - Even-Tov, S.
AU - Kaminsky, E.
AU - Danon, Y. L.
PY - 1994
Y1 - 1994
N2 - Although neurologic manifestations are frequent during childhood shigellosis, their pathogenesis is unclear and controversial. Shiga toxin and other cytotoxins are often implicated, but their effect on neuronal cells has not been determined. We examined the effect of purified Shiga toxin and sonicates of Shigella isolates from children with neurologic symptoms on well-characterized human neuroblastoma cells in vitro. Quantitative determinations showed high cytotoxicity of Shiga toxin on HeLa cells (1.2 x 106 CD50/mg purified toxin), but no effect on LA-N-1, LA-N-5 and IMR neuroblastoma cell lines. Pretreatment with tumor necrosis factor, which increases expression of the Shiga toxin receptor, globotriosyl ceramide, in endothelial cells and enhanced Shiga toxin cytotoxicity, did not affect the susceptibility of neuroblastoma cells to the toxin. Low dilutions (up to 1:16-1:64) of sonicates of Shigella isolates from children with neurologic symptoms caused agglutination of neuroblastoma cells, but no cell killing was observed morphologically. This study shows that Shiga toxin does not exhibit cytotoxic activity on the human neuroblastoma cell lines examined, neither do sonicates of relevant Shigella strains. The mechanism and significance of the agglutination activity on neuroblastoma cells should be further studied.
AB - Although neurologic manifestations are frequent during childhood shigellosis, their pathogenesis is unclear and controversial. Shiga toxin and other cytotoxins are often implicated, but their effect on neuronal cells has not been determined. We examined the effect of purified Shiga toxin and sonicates of Shigella isolates from children with neurologic symptoms on well-characterized human neuroblastoma cells in vitro. Quantitative determinations showed high cytotoxicity of Shiga toxin on HeLa cells (1.2 x 106 CD50/mg purified toxin), but no effect on LA-N-1, LA-N-5 and IMR neuroblastoma cell lines. Pretreatment with tumor necrosis factor, which increases expression of the Shiga toxin receptor, globotriosyl ceramide, in endothelial cells and enhanced Shiga toxin cytotoxicity, did not affect the susceptibility of neuroblastoma cells to the toxin. Low dilutions (up to 1:16-1:64) of sonicates of Shigella isolates from children with neurologic symptoms caused agglutination of neuroblastoma cells, but no cell killing was observed morphologically. This study shows that Shiga toxin does not exhibit cytotoxic activity on the human neuroblastoma cell lines examined, neither do sonicates of relevant Shigella strains. The mechanism and significance of the agglutination activity on neuroblastoma cells should be further studied.
KW - Neuroblastoma cells
KW - Neurologic symptoms
KW - Pediatrics
KW - Shiga toxin
KW - Shigella
UR - http://www.scopus.com/inward/record.url?scp=0028074321&partnerID=8YFLogxK
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C2 - 8045741
AN - SCOPUS:0028074321
SN - 0021-2180
VL - 30
SP - 604
EP - 610
JO - Israel Journal of Medical Sciences
JF - Israel Journal of Medical Sciences
IS - 8
ER -