Abstract
Lymphocytes were studied as vehicles to target the plant toxin ricin, to lymphoid tissue in rats. Ricin-loaded thoracic duct lymphocyte (TDL) migrated normally into lymph nodes (LN) at 0.5 h, but this process was arrested by 3 h after injection. Ricin was successfully targeted to lymphoid tissue as evidenced by a 4-fold increase in ricin-associated radioactivity in LN, a 10-fold increase in the Peyers patches, a doubling in the spleen and a 35% reduction of radioactivity in the liver compared with free ricin. Nevertheless this represented a considerable shortfall in the expected targeting efficiency. The main problem was found to be high in vivo elution of ricin from TDL (70% within 0.5 h of i.v injection). This and other aspects relevant to maximising targeting efficiency are discussed.
Highlights
These radiolabelled lymphocytes recover in vivo following i.v. injection and re-appear in thoracic duct lymph maximally by approximately 18 h later; such cells are referred to as passaged cells and if collected at room temperature and injected within a 4 h period retain their ability to rapidly migrate to lymph nodes (LN)
The uptake of ricin by cells was studied by incubating thoracic duct lymphocyte (TDL) in RPMI + 10% foetal calf serum (FCS) containing '251-ricin (25 yg 10-8 cells) for varying periods
Since galactose side chains present on serum proteins might compete with cells for ricin binding, TDL were incubated with '25I-ricin in a medium containing no FCS
Summary
The toxin Ricinus communis was prepared from the defatted castor bean cake according to the procedures described in detail by Cumber et al (1985). Ricin was kindly supplied by Dr A. Forrester and Professor A.J.S. Davies from the Chester Beatty Cancer Research Laboratory, and at a later stage by Dr P. Thorpe from the Imperial Cancer Research Foundation, London
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