Release of eosinophil granule proteins during IgE-mediated allergic skin reactions

To determine whether the eosinophil (EOS), a prominent component of human allergic skin reactions, releases its potentially pathogenic components in vivo, we appended collection chambers to the bases of unroofed skin blisters and challenged the sites for varying time periods with either pollen antigen (Ag) or buffer (B)-control solutions. In seven sensitive subjects, continuous challenge with pollen Ag consistently induced release of more major basic protein (MBP) and eosinophil-derived neutrophil (EDN) than did B solution. Low levels of both MBP and EDN were observed during the first hour with increased accumulation during the second to fifth hour. Comparison of Ag- versus B-challenged site responses in individual subjects demonstrated significantly higher levels of both MBP and EDN at Ag than at B sites during the second to fifth hour. Levels of both MBP and EDN in the second to fifth hour correlated significantly with histamine release in the same sites in the first hour ( r = 0.66 and 0.83, respectively). Imprints of the skin bases of the chambers after 5 hours demonstrated variable numbers of EOS at the Ag-challenged sites and only occasional EOS at the B-challenged sites; most cells on the skin bases were neutrophils. However, immunofluorescence localization of MBP in biopsy specimens of the blister bases revealed striking extra cellular MBP deposition. These findings indicate that EOS components accumulate in vivo in IgE-mediated human skin reactions, even when prominent EOS accumulation is not visualized, possibly because the EOS are degranulated in the allergic-reaction site. Release of EOS components in these reactions may be linked to earlier mast cell activation. Because cationic EOS granule proteins are toxic for tissues, they could play a pathogenic role in late-phase allergic reactions.