Urokinase-type plasminogen activator inhibits efferocytosis of neutrophils.

American Journal of Respiratory and Critical Care Medicine
Yanping YangEdward Abraham

Abstract

Phagocytosis of apoptotic cells, also called efferocytosis, plays an essential role in the resolution of inflammation. Urokinase-type plasminogen activator (uPA) is a multifunctional protein that has been implicated in inflammatory conditions, including pneumonia and severe infection, which are often accompanied by the development of acute lung injury. However, the role of uPA in modulating efferocytosis of apoptotic neutrophils has not been defined. To characterize the role of uPA in regulation of efferocytosis and to delineate the underlying mechanisms involved in this process. In vitro and in vivo phagocytosis, immunoprecipitation, and Western blotting assays. The phagocytosis of apoptotic neutrophils by macrophages was significantly inhibited by uPA. Mutant uPA lacking the growth factor domain and catalytically inactive uPA had similar inhibitory effects on efferocytosis, as did wild-type uPA. In contrast, absence of the kringle domain abrogated the ability of uPA to diminish efferocytosis. Both the α(V)β₃ integrin and vitronectin seemed to be involved in the inhibition of efferocytosis by uPA. Incubation of macrophages with uPA also diminished activation of the small GTPase Rac-1, which normally occurs during ingestion of ...Continue Reading

References

Sep 22, 1998·The Journal of Experimental Medicine·A E MayK T Preissner
Nov 11, 1999·American Journal of Respiratory and Critical Care Medicine·C Haslett
Aug 10, 2000·The Journal of Experimental Medicine·P R TaylorM J Walport
May 11, 2001·Nature·R S ScottG K Matsushima
Oct 10, 2001·Current Biology : CB·P M HensonV A Fadok
Mar 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anita W RijneveldTom van Der Poll
Aug 13, 2002·The Journal of Biological Chemistry·Taher NassarAbd Al-Roof Higazi
Dec 4, 2002·Nature Reviews. Immunology·John SavillChris Haslett
Mar 7, 2003·American Journal of Physiology. Cell Physiology·Jong Sung ParkEdward Abraham
Apr 12, 2003·Critical Care Medicine·Marcel LeviTom van der Poll
Sep 17, 2003·Critical Care : the Official Journal of the Critical Care Forum·Gustavo Matute-Bello, Thomas R Martin
Mar 17, 2004·Experimental Cell Research·Manolis C DemetriouAnne E Cress
May 15, 2004·Science·J Magarian Blander, Ruslan Medzhitov
Jul 28, 2004·Trends in Immunology·Anna Mondino, Francesco Blasi
Aug 17, 2004·American Journal of Respiratory Cell and Molecular Biology·Michael H LazarThomas H Sisson
Oct 2, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Sandip M KanseKarlheinz Peter
Nov 2, 2004·The European Respiratory Journal·G ChoiT van der Poll
Nov 24, 2004·Cellular and Molecular Life Sciences : CMLS·H Myöhänen, A Vaheri
Jan 6, 2006·Current Directions in Autoimmunity·Rikinari HanayamaShigekazu Nagata
Feb 9, 2006·Cellular and Molecular Life Sciences : CMLS·P Ragno
Mar 15, 2006·Trends in Cell Biology·Yi WuRaymond B Birge
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xue-Qing WangEdward Abraham
Jun 6, 2007·The Journal of Cell Biology·Chris D MadsenNicolai Sidenius
Jun 27, 2007·Journal of Cell Science·Jason M Kinchen, Kodi S Ravichandran
Oct 6, 2007·American Journal of Respiratory and Critical Care Medicine·Stephen M BianchiMoira K B Whyte
Nov 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuko TsurutaEdward Abraham
Nov 27, 2007·Nature Reviews. Immunology·Kodi S Ravichandran, Ulrike Lorenz
Jan 8, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·P M Henson, R M Tuder
Jan 16, 2008·Journal of Thrombosis and Haemostasis : JTH·R RenckensT van der Poll
Mar 14, 2008·Blood·Victoria StepanovaDouglas B Cines
May 22, 2008·Journal of Cell Science·Aurélien G Dupuy, Emmanuelle Caron
Jul 1, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xia ZhaoEdward Abraham
Aug 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Young-Jun ParkEdward Abraham
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gang LiuEdward Abraham

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Citations

May 3, 2011·American Journal of Respiratory and Critical Care Medicine·István Vadász, Jacob I Sznajder
Jan 28, 2012·American Journal of Respiratory Cell and Molecular Biology·Hong-Beom BaeEdward Abraham
Apr 13, 2012·Molecular Medicine·Arnaud FriggeriGang Liu
Feb 24, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Helena EnocssonJonas Wetterö
Jun 25, 2013·The Journal of Pathology·James N FullertonDerek W Gilroy
Apr 20, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arnaud FriggeriEdward Abraham
Mar 16, 2017·Journal of Leukocyte Biology·Ioannis KourtzelisTriantafyllos Chavakis
Jan 25, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong-Beom BaeJaroslaw W Zmijewski

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