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 of allergic inflammation and is associated with infiltration of neutrophils, eosinophils, T cells, and macrophages. The mechanisms controlling the resolution of allergic inflammatory processes and the fate of infiltrating cells are uncertain. We observed that both the magnitude of the late-phase response and the numbers of infiltrating neutrophils and eosinophils peaked at 6 hr, persisted for 48 hr, but resolved completely by 7 days. In contrast, T-cell and macrophage numbers peaked between 24 and 72 hr after allergen challenge and persisted for up to 7 days. By using the techniques of terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine 5'-triphosphate (dUTP) nickend-labeling (TUNEL) and by combining TUNEL with immunohistochemistry, we tested the hypothesis that the resolution of the late-phase response is associated with apoptosis of neutrophils and eosinophils, with subsequent engulfment of apoptotic cells and apoptotic bodies by tissue macrophages. As the cutaneous late-phase response resolved, there was a progressive increase (peaking at 72 hr) in the total numbers of TUNEL-positive (TUNEL+) cells and in the numbers of macrophages that had engulfed apoptotic cells and bodies. The majority of TUNEL+ cells were identified as neutrophils and eosinophils. In contrast, very little apoptosis was associated with T cells or macrophages. These experiments represent a novel demonstration of cell type-specific apoptosis in vivo in human allergic inflammatory tissue and suggest that phagocytosis by macrophages of apoptotic neutrophils and eosinophils may be a mechanism that regulates resolution of the atopic allergic inflammatory response.
Ying
S
S
Imperial College School of Medicine, National Heart & Lung Institute, London, U.K.
Meng
Q
Q
Taborda-Barata
L
L
Kay
A B
AB
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D017209:Apoptosis / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D011058:Pollen
D000485:Allergens