Acceleration of Human Neutrophil Apoptosis by TRAIL

• Published in: The Journal of immunology (1950) Vol. 170; no. 2; pp. 1027 - 1033
• Main Authors: Renshaw, Stephen A, Parmar, Jasvir S, Singleton, Vanessa, Rowe, Sarah J, Dockrell, David H, Dower, Steven K, Bingle, Colin D, Chilvers, Edwin R, Whyte, Moira K. B
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.2003
• Subjects: Apoptosis - immunology; Apoptosis Regulatory Proteins; Cells, Cultured; Fas Ligand Protein; fas Receptor - immunology; fas Receptor - metabolism; GPI-Linked Proteins; Humans; Leucine Zippers - immunology; Ligands; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Neutrophils - cytology; Neutrophils - immunology; Neutrophils - metabolism; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor - biosynthesis; Receptors, Tumor Necrosis Factor, Member 10c; Recombinant Fusion Proteins; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Signal Transduction - immunology; Time Factors; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor Decoy Receptors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.2.1027

Neutrophil granulocytes have a short lifespan, with their survival limited by a constitutive program of apoptosis. Acceleration of neutrophil apoptosis following ligation of the Fas death receptor is well-documented and TNF-alpha also has a transient proapoptotic effect. We have studied the role of the death receptor ligand TRAIL in human neutrophils. We identified the presence of mRNAs for TRAIL, TRAIL-R2, and TRAIL-R3, and cell surface expression of TRAIL-R2 and -R3 in neutrophil populations. Neutrophil apoptosis is specifically accelerated by exposure to a leucine zipper-tagged form of TRAIL, which mimics cell surface TRAIL. Using blocking Abs to TRAIL receptors, specifically TRAIL-R2, and a TRAIL-R1:FcR fusion protein, we have excluded a role for TRAIL in regulating constitutive neutrophil apoptosis. No additional proapoptotic effect of leucine zipper TRAIL was identified following TRAIL treatment of neutrophils in the presence of gliotoxin, an inhibitor of NF-kappaB, suggesting TRAIL does not activate NF-kappaB in human neutrophils. TRAIL treatment of human neutrophils did not induce a chemotactic response. The susceptibility of neutrophils to TRAIL-mediated apoptosis suggests a role for TRAIL in the regulation of inflammation and may provide a mechanism for clearance of neutrophils from sites of inflammation.