Share this post on:

from toxin-mediated death from either Stx1-S or the more medically relevant Stx2a. While Mukhopadhyay and Linstedt reported that manganese is cleared from the mice within hours, they show protection against intoxication with a once daily injection of Mn2+ five days prior to and everyday post challenge with Stx1-S, at approximately 500 ng Stx1-S per mouse. Using this same model with CD-1 mice, in our study all of the mice died on either day 2 or day 3 post-challenge. No difference in body weight was seen at 48 hours after challenge, suggesting that increased time to death does not reflect protection. The use of different experimental systems could account for the failure to reproduce the reported results. In human disease, Stx is known to target three different cell types which naturally express globotriaosylceramide, the glycolipid receptor for Stx: kidney cells, endothelial cells and neurons. The female reproductive tract, where HeLa cells originated, has not been reported to be targeted by Stx. HeLa are likely susceptible to Stx because upregulation of Gb3 expression is common in cancer cells. Nevertheless, HeLa cells are still more resistant to Stx than Vero cells. Mukhopadhyay and Linstedt used HeLa cells transfected to express Gb3 synthase, to increase expression of the Gb3 receptor, and demonstrated that Stx resistance is due to altered intracellular trafficking in HeLa cells. However, it is known that Stx uses different pathways to enter cells, and it is possible that manganese does not alter Stx trafficking in its natural target cells, including kidney cells. MnCl2 was also reported to protect BALB/c mice from Stx1-S. We did not observe manganese protection from either Stx1-S or Stx2a in the outbred CD-1 mouse line. BALB/c mice are null mutants for Slc11a1, an H + /divalent cation antiporter expressed by phagocytes with a high affinity for Mn2+. It is not clear if this genetic DEL-22379 mutation could have been a factor in the observed protection against Stx1-S, but outbred CD-1 mice are likely to more closely reflect 1411977-95-1 normal human physiologic responses to Mn2+. In addition, Stx2a, not Stx1-S, is most associated with development of fatal human disease, and the failure to observe protection form Stx2a is significan

Share this post on:

Author: calcimimeticagent