Published ahead of print on June 30, 2004, doi:10.1164/rccm.200402-240OC Am. J. Respir. Crit. Care Med., Volume 170, Number 7, October 2004, 742-747 A more recent version of this article appeared on October 1, 2004
Submitted on February 25, 2004 Occurrence of Apoptosis, Secondary Necrosis and Cytolysis in Eosinophilic Nasal PolypsLena Uller1*,1 Department of Physiological Sciences, Lund University, Lund, Sweden, 2 Department of ENT, Lund University Hospital, Lund, Sweden, 3 Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden * To whom correspondence should be addressed. 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 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 ribonuclease nick end labelling). Of >3000 examined tissue eosinophils 110 were caspase cleavage-positive but only one was apoptotic. Transmission electron microscopy analysis of >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 clearance of eosinophils from nasal polyps largely occurs through non-apoptosis 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, PARP, TUNEL, Epithelium
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