Targeting Talk: Suicide Transport and Immunolesioning

What is immunolesioning?

Immunolesioning is a technique for making highly selective cellular lesions using immunotoxins. The immunotoxins consist of a monoclonal antibody to a cell surface molecule and a toxic effect or moiety such as saporin, a ribosome-inactivating protein. The selectivity of the lesion made with this technique depends on the selective expression of the target surface molecule on the cells of interest. Immunotoxins may be applied in a projection field where the toxin is taken up by axon terminals and retrogradely transported to the cell bodies resulting in destruction of an entire neuron. Other routes of application include: directly in vicinity of cell bodies, into CSF, and into culture supernatant.

What is suicide transport?

Suicide transport is an anatomically selective neural lesioning technique that relies on axonal uptake of a toxin that is retrogradely transported to the cell body resulting in destruction of the entire neuron. Examples include the toxic lectins [ricin, volkensin] and immunotoxins [192-Saporin (192-IgG-SAP): Cat. #IT-01, OX7-SAP: Cat. #IT-02, Anti-DBH-SAP: Cat. #IT-03]. The goal of using this technique is to selectively destroy a group of neurons based on where the corresponding axons project.

How do I administer a targeted toxin to achieve suicide transport?

Generally, precise control of dose and location of injection is important in suicide transport experiments. Consequently, pressure microinjection is the preferred method of toxin delivery. In the peripheral nervous system, subepineurial injection (inside the connective tissue sheath of a peripheral nerve) works well. Within the CNS, stereotactic techniques are typically used to deliver toxin to the desired target.

References

  1. Wiley RG, Lappi DA (1994) Suicide Transport and Immunolesioning. Houston, R.G. Landes.
  2. Helke CJ, Charlton CG, Wiley RG (1985) Suicide transport of ricin demonstrates the presence of substance P receptors on medullary somatic and autonomic motor neurons. Brain Res 328:190-195.
  3. Contestabile A, Fasolo A, Virgili M, Migani P, Villani L, Stirpe F (1990) Anatomical and neurochemical evidence for suicide transport of a toxic lectin, volkensin, injected in the rat dorsal hippocampus. Brain Res 537:279-286.
  4. Panaglos MN, Francis PT, Pearson RCA, Middlemiss DN, Bowen DM (1991) Destruction of a sub-population of cortical neurons by suicide transport of volkensin, a lectin from Adenia volkensii. J Neurosci Meth 40:17-29.
  5. Wiley RG (1992) Neural lesioning with ribosomeinactivating proteins: suicide transport and immunolesioning. Trends in Neurosci 15:285-290.
  6. Roberts RC, Harrison MB, Francis SMN, Wiley RG (1993) Differential effects of suicide transport lesions of the striatonigral or striatopallidal pathways on subsets of striatal neurons. Exp Neurol 124:242-252.
  7. Wiley RG, Stirpe F, Thorpe P, Oeltmann TN (1989) Neuronotoxic effects of monoclonal anti-Thy 1 antibody (OX7) coupled to the ribosome inactivating protein, saporin, as studied by suicide transport experiments in the rat. Brain Res 505:44-54.
  8. Wiley RG, Kline IR (2000) Neuronal lesioning with axonally transported toxins. J Neurosci Meth 103(1):73-82.

 
See also: Targeted Toxins Catalog