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Occurrence of Apoptosis, Secondary Necrosis, and Cytolysis in Eosinophilic Nasal Polyps

Department of Physiological Sciences; Department of Otorhinolaryngology, Head and Neck Surgery; and Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden

Correspondence and requests for reprints should be addressed to Lena Uller, M.Sc., Department of Physiological Sciences, BMC F10, Lund University, 221 84 Lund, Sweden. E-mail: lena.uller{at}mphy.lu.se

The paradigm states that inflammatory cells disappear from airway tissues through apoptosis and phagocytosis. However, cells may also be cleared through primary cytolysis, necrosis secondary to apoptosis, or transepithelial migration. This study examines the occurrence of apoptosis, secondary necrosis, and cytolysis of eosinophils in human nasal polyps in vivo and blood eosinophils in vitro. Eosinophils abounded in subepithelium and in paracellular epithelial pathways. Macrophages commonly occurred but without engulfed eosinophils. Scattered cells, including epithelial cells, were stained by antibody to the caspase cleavage product of poly(ADP-ribose) polymerase. Few cells were apoptotic (stained by terminal deoxy RNase nick end labeling). Of more than 3,000 examined tissue eosinophils, 110 were caspase cleavage positive, but only one was apoptotic. Transmission electron microscopy analysis of more than 500 eosinophils revealed viable and cytolytic eosinophils but not apoptosis, secondary necrosis, or engulfment of eosinophils. Plasma cells but neither epithelial cells nor eosinophils exhibited apoptotic ultrastructural morphology. Eosinophils in vitro exhibited different stages of apoptosis, ending with secondary necrosis distinct from in vivo eosinophil cytolysis. Our results show that the clearance of eosinophils from nasal polyps largely occurs through nonapoptosis pathways, including cytolysis and paraepithelial migration, and they challenge the belief that apoptosis is important for clearance of eosinophils from respiratory tissues.

Key Words: electron microscopy • epithelium • poly(ADP-ribose) polymerase • terminal deoxy RNase nick end labeling

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