Type 1 hypersensitivity reactions in reconstructed tissues using syngeneic cell types.

Abstract

1. Type 1 hypersensitivity reactions in response to antigen challenge have been measured as short circuit current (SCC) responses in reconstructed tissues consisting of syngeneic cell types. 2. In all instances reconstructed tissues consisted of an epithelial monolayer grown on collagen-coated Millipore filters and a pad of peritoneal cells. Monolayers were formed of either HCA-7 or HCA-7-Col 1 cells derived from a human adenocarcinoma. Peritoneal cells were derived from rats or guinea-pigs sensitized to either ovalbumin or beta-lactoglobulin. 3. The SCC responses of the monolayers were dependent upon the 'concentration' of peritoneal cells in the reconstructed tissue. The threshold concentration was 0.4 X 10(6) cells when rat peritoneal cells are combined with an epithelial monolayer of 0.2 cm2. 4. The SCC responses in response to antigen challenge were selectively inhibited by the H1-receptor antagonist, mepyramine. Similarly the effects of exogenously applied histamine were antagonised by mepyramine. 5. The responses to antigen challenge were not inhibited by tetrodotoxin in reconstructed tissues. This result is in contrast to that with isolated intestinal epithelia from sensitized animals where tetrodotoxin inhibits the SCC responses to external field stimulation and to challenge with antigens. The consequences of these results for understanding the mechanisms of epithelial Type 1 hypersensitivity reactions are discussed. Suggestions are made to illustrate how the methods developed here may be employed to ask questions about the nature of mediators released and the types of cell responsible in human disease conditions.