Antigen aerosols induce lung nonresponsiveness

Guinea pigs intranasally dusted with ragweed pollen (RW) for one month went into anaphylaxis in ragweed extract aerosol (RWEA). Animals which received RWEA pretreatment for one month before nasal dusting with RW pollen were nonresponsive to RWEA. The purpose of this study was to define the mechanism of nonresponsiveness. The protocol for producing either sensitivity or nonresponsiveness was applicable to another antigen, bovine serum albumin (BSA). Antibody blocking passive cutaneous anaphylaxis (PCA) in passively sensitized animals was demonstrable in BSA nonresponder serum. However, the blocking antibody probably was not responsible for the nonresponsiveness because BSA nonresponder serum was also able to sensitize passively the skin and lungs of normal recipients. Also nonresponsiveness was not due to the swallowing of antigen because feeding antigen inhibited synthesis of sensitizing antibody and precipitating antibody both of which were present in high titers in nonresponders. Sensitive guinea pig lungs contained nearly twice as much histamine as normal and nonresponder lungs. However, normal and nonresponders went into anaphylaxis at the same time in an aerosol of compound 48/80. These results suggest that the mechanism of nonresponsiveness produced by pretreatment with antigen aerosols might be due to a modification in antigen reactivity of the lung mast cells rather than to alterations in the mediators of anaphylaxis.