Induction of murine reaginic antibodies by toluene diisocyanate. An animal model of immediate hypersensitivity reactions to isocyanates.
Tse-CS; Chen-SE; Bernstein-IL
Am Rev Respir Dis 1979 Oct; 120(4):829-835
A murine model was developed for homocytotropic antibodies (HCA) induced by toluene-diisocyanate (26471625) (TDI) in C57B1-mice, DBA- mice, and HRS/J-mice. Protein conjugates were prepared using TDI, human serum albumin (HSA), bovine serum albumin (BSA), or ovalbumin (OVA). Chemical assays were performed to determine the moles of isocyanate bound to protein as a function of reaction time. Mice were intraperitoneally immunized with 100 micrograms (microg) of the various conjugates or carrier proteins mixed with aluminum- hydroxide. Immunologic reactivity of animals immunized with the various carrier proteins was assessed in sera obtained 14 days after primary immunization. The same doses of homologous antigen and aluminum-hydroxide were given 28 to 35 days after the initial injection to determine anamnestic effects. Hapten specificity of HCA was tested by passive cutaneous anaphylactic (PCA) reactions in response to intravenous challenge. Sera from mice immunized with 100microg of unconjugated HSA, BSA, or OVA proteins demonstrated HCA titers of 1 to 40 after challenge. Immunoglobulin-E antibody titers ranging from 1 to 57 to 1 to 113 were obtained when sera from mice immunized with TDI/HSA, TDI/BSA, and TDI/OVA were challenged with respective homologous hapten protein conjugates. Lower PCA titers were obtained when the same sera were challenged with conjugates of TDI coupled with heterologous carriers. There was low cross reacting among conjugates. Carrier and hapten specific effects were demonstrated. The authors conclude that moderately substituted and mono functionally TDI bound proteins are potent immunogens for the production of reaginic antibodies in susceptible strains of mice. The animal model of HCA induced by chemically well characterized protein conjugates of TDI is reproducible.
NIOSH-Publication; NIOSH-Grant; Synthetic-rubbers; Analytical-models; Immune-reaction; Animal-studies; Hypersensitivity; Industrial-chemicals; Industrial-medicine; Medical-research
Internal Medicine University of Cincinnati 231 Bethesda Avenue Cincinnati, Ohio 45267
American Review of Respiratory Disease
University of Cincinnati, Cincinnati, Ohio