ASSOCIATION OF APOPTOSIS OF NEUTROPHILS AND EOSINOPHILS AND THEIR INGESTION BY MACROPHAGES WITH RESOLUTION OF THE ALLERGEN-INDUCED CUTANEOUS LATE-PHASE RESPONSE IN ATOPIC HUMAN-SUBJECTS

The allergen-induced cutaneous late-phase response serves as a model o f allergic inflammation and is associated with infiltration of neutrop hils, eosinophils, T cells, and macrophages. The mechanisms controllin g the resolution of allergic inflammatory processes and the fate of in filtrating cells are uncertain. We observed that both the magnitude of the late-phase response and the numbers of infiltrating neutrophils a nd eosinophils peaked at 6 hr, persisted for 48 hr, but resolved compl etely by 7 days. In contrast, T-cell and macrophage numbers peaked bet ween 24 and 72 hr after allergen challenge and persisted for up to 7 d ays. By using the techniques of terminal deoxynucleotidyl transferase- mediated biotin-deoxyuridine 5'-triphosphate (dUTP) nick-end-labeling (TUNEL) and by combining TUNEL with immunohistochemistry, we tested th e hypothesis that the resolution of the late-phase response is associa ted with apoptosis of neutrophils and eosinophils, with subsequent eng ulfment of apoptotic cells and apoptotic bodies by tissue macrophages. As the cutaneous late-phase response resolved, there was a progressiv e increase (peaking at 72 hr) in the total numbers of TUNEL-positive ( TUNEL(+)) cells and in the numbers of macrophages that had engulfed ap optotic cells and bodies. The majority of TUNEL(+) cells were identifi ed as neutrophils and eosinophils. In contrast, very little apoptosis was associated with T cells or macrophages. These experiments represen t a novel demonstration of cell type-specific apoptosis in vivo in hum an allergic inflammatory tissue and suggest that phagocytosis by macro phages of apoptotic neutrophils and eosinophils may be a mechanism tha t regulates resolution of the atopic allergic inflammatory response.