Fas-mediated apoptosis in cultured human eosinophils

• Published in: Blood Vol. 87; no. 7; pp. 2822 - 2830
• Main Authors: DRUILHE, A, CAI, Z, HAILE, S, CHOUAIB, S, PRETOLANI, M
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 01-04-1996
• Subjects: Ageing, cell death; Apoptosis - immunology; Base Sequence; Biological and medical sciences; Cell physiology; Eosinophils - immunology; Eosinophils - pathology; fas Receptor - biosynthesis; fas Receptor - immunology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Molecular and cellular biology; Molecular Sequence Data; Human; Cell culture; Leukocyte; Cell death; Cytokine; Gene expression; In vitro; Eosinophil; Apoptosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v87.7.2822.bloodjournal8772822

Previous studies have shown that cytokine-dependent eosinophils undergo apoptosis, yet the mechanisms governing this phenomenon remain obscure. Fas antigen is a transmembrane glycoprotein belonging to the tumor necrosis factor receptor family. Cross-linking of Fas antigen in numerous cell types leads to apoptosis. In the present study, we examined the potential role of Fas antigen in the apoptosis of purified blood eosinophils from healthy donors. Cytokine-deprived eosinophils exhibited a time-dependent loss in viability, accompanied by an increase in the number of apoptotic nuclei and in the expression of Fas antigen and its mRNA, as shown by flow cytometry and reverse transcriptase-polymerase chain reaction, respectively. Cross-linking of Fas antigen with an agonistic anti-Fas monoclonal antibody (MoAb) induced a dose- and time-dependent increase in the number of apoptotic nuclei. Furthermore, using an in vitro coculture system, we showed engulfment of anti-Fas MoAb-treated eosinophils by monocyte-derived macrophages. Finally, incubation of eosinophils with the corticosteroid, dexamethasone, induced apoptosis and augmented that triggered by anti-Fas MoAb. Together, these observations suggest that Fas antigen expression and activation is involved in the apoptosis of human eosinophils and may contribute to the resolution of inflammatory allergic reactions in which eosinophil accumulation is a prominent feature.