INDUCTION OF MURINE REAGINIC ANTIBODIES BY TOLUENE DIISOCYANATE - ANIMAL-MODEL OF IMMEDIATE HYPERSENSITIVITY REACTIONS TO ISOCYANATES

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Abstract
To clarify some of the controversial aspects of immune responses ascribed to isocyanates in exposed workers and in laboratory animals, this investigation sought to establish an analogous homocytotropic antibody model in mice immunized with well-characterized isocyanate-protein conjugates. Toluene diisocyanate [TDI] was conjugated to serum albumins of human, bovine and ovine species under controlled conditions, and the amount of ligand bound to various proteins was determined spectrophotometrically. Strain B6D2F1 mice were immunized and boosted 28 days later with 100 .mu.g of TDI-conjugated proteins or unconjugated proteins plus 1 mg of alum. Sera were assessed for 48 h passive cutaneous anaphylaxis in hairless mice. Sera from mice immunized with TDI-conjugated human, bovine or ovine serum albumin demonstrated passive cutaneous anaphylaxis titers of 1:57 of higher when challenged with homologous conjugates and somewhat lower titers (range, < 1:5-1:20) after reactions with heterologous conjugates. Mice immunized with carrier proteins (human, bovine or ovine serum albumin) alone produced homocytotropic antibody (1:40) to corresponding unconjugated proteins and homologous TDI conjugates (1:5-1:10) but not to heterologous carrier proteins or TDI conjugates. Hapten specificity of these reactions was proved by appropriate absorption experiments. Passive cutaneous anaphylatic activity in sera containing TDI-specific antibodies was completely abolished after heating at 56.degree. C for 1 h. The murine model of isocyanate-induced homocytotropic antibody is a convenient method of assessing reliability and reproducibility of isocyanate adducts to be used for immunologic investigations of suspected human hypersensitivity to TDI.