Association of Synthetic Polypeptides with Ribonucleic Acid of Immunocompetent Tissues

Abstract

Abstract The association of 125I-labeled synthetic polypeptides with ribonucleic acid (RNA) of rabbit peritoneal exudate (p.e.) cells in in vitro systems has been shown to be a cell-mediated reaction, related to the charge, state of aggregation and optical configuration of the polymer. Although slightly higher levels of several D-amino acid polymers were associated with p.e. cells in in vitro systems, the concentrations of p.e. cell RNA-associated 125I-polypeptides of the L-configuration were significantly greater than the D-form. Intraperitoneal administration of the L or D configuration of the polymer—(Glu60Ala30Tyr10)n—(GAT) to oil-stimulated rabbits resulted in p.e. cell uptake and RNA-association of both isomeric polypeptide forms. Whereas the levels of cellular and RNA-associated L-polypeptide declined rapidly over a 24-hr period, the respective concentrations of the D-polymer significantly increased during this period. Similar observations were noted following i.v. administration of D- or L-GAT to normal or hyperimmune animals. Levels of 125I L-GAT declined rapidly over a 24-hr period in kidney, bone marrow, liver, spleen and lymph node. Tissue and RNA-associated levels of 125I D-GAT remained fairly constant for 7 days after administration. There was essentially no correlation between in vitro and in vivo studies with respect to formation of RNA-antigen complexes. The significance of tissue distribution and polypeptide metabolism in the intact animal, its role in the formation of RNA-antigen complexes and induction of the immune response appear to preclude any oversimplification in attempting to correlate data from a unicom-partmental in vitro cell system with the dynamic multicompartmental in vivo systems.