title: Histone H2B as a functionally important plasminogen receptor on macrophages.
abstract: Plasminogen (Plg) facilitates inflammatory cell recruitment, a function that depends upon its binding to Plg receptors (Plg-Rs). However, the Plg-Rs that are critical for cell migration are not well defined. Three previously characterized Plg-Rs (alpha-enolase, annexin 2, and p11) and a recently identified Plg-R (histone H2B [H2B]) were assessed for their contribution to Plg binding and function on macrophages. Two murine macrophage cell lines (RAW 264.7 and J774A.1) and mouse peritoneal macrophages induced by thioglycollate were analyzed. All 4 Plg-Rs were present on the surface of these cells and showed enhanced expression on the thioglycollate-induced macrophages compared with peripheral blood monocytes. Using blocking Fab fragments to each Plg-R, H2B supported approximately 50% of the Plg binding capacity, whereas the other Plg-Rs contributed less than 25%. Anti-H2B Fab also demonstrated a major role of this Plg-R in plasmin generation and matrix invasion. When mice were treated intravenously with anti-H2B Fab, peritoneal macrophage recruitment in response to thioglycollate was reduced by approximately 45% at 24, 48, and 72 hours, with no effect on blood monocyte levels. Taken together, these data suggest that multiple Plg-Rs do contribute to Plg binding to macrophages, and among these, H2B plays a very prominent and functionally important role.
authors: Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic, OH, USA.
authors: Riku
authors: R
authors: Das
authors: Tim
authors: T
authors: Burke
authors: Edward F
authors: EF
authors: Plow
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002460:Cell Line; D006657:Histones / Q000378:metabolism / Q000502:physiology*; D007249:Inflammation / Q000209:etiology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator
chemical_list: D000954:Antigens, Surface; D006657:Histones; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen
references: Thromb Haemost. 1999 Sep;82 Suppl 1:4-7
references: 10695477
references: Methods. 2000 Jun;21(2):103-10
references: 10816371
references: Blood. 2001 Feb 1;97(3):777-84
references: 11157497
references: Blood. 2001 Feb 15;97(4):1070-8
references: 11159539
references: J Biol Chem. 2001 Jun 1;276(22):19078-83
references: 11264290
references: J Hepatol. 2001 Dec;35(6):781-9
references: 11738106
references: J Biol Chem. 2002 Sep 13;277(37):33564-70
references: 12087108
references: J Clin Invest. 2002 Nov;110(9):1275-82
references: 12417566
references: Am J Hematol. 2003 Apr;72(4):234-42
references: 12666133
references: J Biol Chem. 2003 Jul 11;278(28):25577-84
references: 12730231
references: J Thromb Haemost. 2003 Aug;1(8):1683-7
references: 12911578
references: Thromb Haemost. 2003 Oct;90(4):724-33
references: 14515195
references: Blood. 2003 Oct 15;102(8):2819-27
references: 12829586
references: Curr Drug Targets Inflamm Allergy. 2003 Sep;2(3):257-65
references: 14561160
references: J Immunol. 2004 Apr 1;172(7):4410-7
references: 15034056
references: J Biol Chem. 2004 Apr 23;279(17):18063-72
references: 14769799
references: J Thromb Haemost. 2004 Oct;2(10):1798-805
references: 15456492
references: J Pathol Bacteriol. 1966 Apr;91(2):575-87
references: 5950612
references: Cancer Res. 1982 Apr;42(4):1530-6
references: 6949641
references: J Clin Invest. 1985 Sep;76(3):991-8
references: 3876357
references: J Cell Biol. 1986 Dec;103(6 Pt 1):2411-20
references: 3023400
references: Cell Immunol. 1989 Jan;118(1):178-91
references: 2910501
references: J Cell Biol. 1990 Oct;111(4):1673-83
references: 2170426
references: Biochemistry. 1991 Feb 12;30(6):1682-91
references: 1847072
references: J Biol Chem. 1991 Jul 5;266(19):12329-36
references: 1712017
references: J Biol Chem. 1991 Jul 5;266(19):12752-8
references: 1829461
references: Arch Biochem Biophys. 1991 May 1;286(2):625-8
references: 1654795
references: Blood. 1991 Nov 1;78(9):2318-27
references: 1932747
references: J Leukoc Biol. 1994 Mar;55(3):410-22
references: 7509844
references: J Biol Chem. 1994 Aug 19;269(33):21191-7
references: 8063740
references: J Biol Chem. 1994 Aug 19;269(33):21198-203
references: 8063741
references: J Neurochem. 1994 Dec;63(6):2048-57
references: 7964722
references: Thromb Res. 1994 Aug 15;75(4):371-81
references: 7997975
references: Eur J Biochem. 1995 Jan 15;227(1-2):407-15
references: 7851415
references: Am J Clin Pathol. 1995 Apr;103(4):466-71
references: 7726145
references: FASEB J. 1995 Jul;9(10):939-45
references: 7615163
references: Biochem Pharmacol. 1995 Jul 31;50(3):299-309
references: 7646532
references: N Engl J Med. 2005 Apr 21;352(16):1685-95
references: 15843671
references: Br J Haematol. 2005 Nov;131(4):553-4; author reply 554-6
references: 16281949
references: Biochemistry. 2006 Aug 8;45(31):9463-74
references: 16878981
references: J Clin Invest. 1995 Nov;96(5):2534-8
references: 7593646
references: Thromb Haemost. 1995 Jul;74(1):294-301
references: 8578475
references: J Clin Invest. 1997 Jan 15;99(2):200-8
references: 9005988
references: Blood. 1997 Jun 15;89(12):4574-83
references: 9192782
references: Circ Res. 1997 Nov;81(5):829-39
references: 9351457
references: Blood. 1998 Mar 15;91(6):2005-9
references: 9490683
references: Br J Cancer. 1998 May;77(10):1586-97
references: 9635833
references: J Clin Invest. 1998 Jul 15;102(2):283-93
references: 9664069
references: J Exp Med. 1998 Sep 21;188(6):1029-37
references: 9743521
references: J Clin Invest. 1998 Nov 15;102(10):1788-97
references: 9819364
references: Blood. 1999 Jun 1;93(11):3839-46
references: 10339491
references: Exp Cell Res. 2005 Feb 1;303(1):22-31
references: 15572024
references: J Biol Chem. 2005 Jan 14;280(2):1336-45
references: 15485828
references: Curr Pharm Des. 2005;11(5):569-80
references: 15720276