Aminopeptidase N (CD13) regulates tumor necrosis factor-alpha-induced apoptosis in human neutrophils

The Journal of Biological Chemistry
Andrew S CowburnE R Chilvers

Abstract

Neutrophil apoptosis plays a central role in the resolution of granulocytic inflammation. We have shown previously that tumor necrosis factor-alpha (TNFalpha) enhances the rate of neutrophil apoptosis at early time points via a mechanism involving both TNF receptor (TNFR) I and TNFRII. Here we reveal a marked but consistent variation in the magnitude of the pro-apoptotic effect of TNFalpha in neutrophils isolated from healthy donors, and we show that inhibition of cell surface aminopeptidase N (APN) using actinonin, bestatin, or inhibitory peptides significantly enhanced the efficacy of TNFalpha-induced killing. Notably, an inverse correlation is shown to exist between neutrophil APN activity and the sensitivity of donor cells to TNFalpha-induced apoptosis. Inhibition of cell surface APN appears to interfere with the shedding of TNFRI, and as a consequence results in augmented TNFalpha-induced apoptosis, cell polarization, and TNFalpha-primed, formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst. Of note, actinonin and bestatin had no effect on TNFRII expression under resting or TNFalpha-stimulated conditions and did not alter CXCRI or CXCRII expression. These data suggest significant variation in the activity of ...Continue Reading

References

Jan 1, 1991·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·G Mathé
Aug 1, 1990·The Journal of Experimental Medicine·F Porteu, C Nathan
Apr 1, 1989·The Journal of Clinical Investigation·A T LookS C Peiper
Nov 1, 1993·Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy·J E TalmadgeG A Perry
Mar 17, 1995·Biochemical and Biophysical Research Communications·Y XuD A Scheinberg
Apr 14, 1995·The Journal of Biological Chemistry·L H Shapiro
Jun 1, 1993·International Immunology·Y TakedaF Sendo
Jun 1, 1996·Journal of Leukocyte Biology·D ChitnisR A Winchurch
Sep 1, 1996·Mammalian Genome : Official Journal of the International Mammalian Genome Society·C LercheH Sjöström
Jan 1, 1996·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·K EzawaK Dobashi
Jan 1, 1997·British Medical Bulletin·C Haslett
Dec 31, 1997·American Journal of Respiratory and Critical Care Medicine·G Matute-BelloT R Martin
Feb 6, 1999·The Journal of Biological Chemistry·C WardA G Rossi
Mar 31, 1999·Immunology Today·D RiemannJ Langner
Apr 15, 1999·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·V H van der Velden, A R Hulsmann
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P DriP Patriarca
Feb 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·G SalamoneJ R Geffner
Jun 21, 2001·Clinical Immunology : the Official Journal of the Clinical Immunology Society·M AlemánM C Sasiain
Jul 24, 2001·Current Drug Metabolism·O A Scornik, V Botbol
Dec 18, 2001·International Journal of Cancer. Journal International Du Cancer·K SekineK Nishikawa
Sep 26, 2003·The Journal of Biological Chemistry·Nenad PetrovicLinda H Shapiro
Nov 25, 2003·Clinical and Experimental Immunology·G HuschakD Riemann
May 18, 2005·Cancer Letters·Mirjana GrujicMetka Renko

❮ Previous
Next ❯

Citations

Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Liliana Guzman-RojasRenata Pasqualini
Feb 16, 2010·Plant Physiology·Fazeeda N HoseinAngus S Murphy
Mar 25, 2014·Frontiers in Cellular and Infection Microbiology·Robert V Schoborg, Nicole Borel
Apr 5, 2008·International Immunopharmacology·Jelka GabrilovacBarbara Cupić
Oct 11, 2007·American Journal of Hematology·Hongbo R Luo, Fabien Loison
Sep 24, 2009·Journal of Clinical Laboratory Analysis·Roger S RileyJonathan M Ben-Ezra
Jan 25, 2008·American Journal of Physiology. Renal Physiology·Lorena BlancoAdolfo Varona
May 14, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marion PiedferBrigitte Bauvois
Dec 19, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chenyang LuDavid A Fox
Mar 23, 2021·Frontiers in Immunology·Erandi Pérez-FigueroaCarmen Maldonado-Bernal
May 4, 2020·Experimental and Molecular Pathology·Barbara Lisowska-MyjakEwa Skarżyńska

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Caspases in Metabolic Diseases

Caspases, the family of cysteine proteases are involved in programmed cell death, but their role in metabolic diseases, inflammation and immunity has been of interested. Discover the latest research on caspases in metabolic diseases here.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis