HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Plescia, J. Articles by Altieri, D. C. Search for Related Content PubMed PubMed Citation Articles by Plescia, J. Articles by Altieri, D. C. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 32, 20372-20377, August 7, 1998

Molecular Identification of the Cross-reacting Epitope on _M2 Integrin I Domain Recognized by Anti-_IIb3 Monoclonal Antibody 7E3 and Its Involvement in Leukocyte Adherence

Janet Plescia, Michael S. Conte, Guy VanMeter, Grazia Ambrosini, and Dario C. Altieri

From the Department of Pathology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536 and the  Division of Vascular Surgery, Brigham and Women's Hospital, Harvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts 02115

The monoclonal antibody (mAb) 7E3 directed to the platelet integrin _IIb3 was tested for its cross-reactivity with the homologous leukocyte integrin _M2. Nested recombinant fragments of _M I domain were expressed as glutathione S-transferase fusion proteins and analyzed for antibody recognition. In enzyme-linked immunosorbent assay, mAb 7E3 bound _M I domain fragments containing the amino-terminal sequence Cys¹²⁸-Ser¹⁷², whereas the carboxyl-terminal region Leu¹⁷³-Pro²⁹¹ was ineffective. A synthetic peptide designated R1.1 and duplicating the _M sequence G¹²⁷CPQEDSDIAFLIDGSGSIIPHDF¹⁵⁰ bound mAb 7E3. In contrast, the adjacent _M region F¹⁵⁰RRMKEFVSTVMEQLKKSKTLFS¹⁷² or a control peptide with a scrambled R1.1 sequence was not recognized by mAb 7E3. Binding of mAb 7E3 to _M I domain blocked monocyte and neutrophil adhesion to immobilized fibrinogen and fibrinogen-dependent leukocyte-endothelium bridging, indistinguishably from bona fide anti-₂ mAb IB4. In contrast, leukocyte binding to stable transfectants expressing intercellular adhesion molecule-1 was not affected by mAb 7E3. Balloon-mediated injury of iliofemoral arteries in rabbits resulted in prominent deposition of fibrinogen and increased monocyte adhesion to the injured vessel, in a reaction inhibited by mAb 7E3, but unaffected by control mAb 14E11. Through its cross-reactivity between _IIb3 and _M2, mAb 7E3 may initiate a new class of integrin antagonists, capable of simultaneously targeting platelet and leukocyte adhesion mechanisms in vascular injury.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. N. Seshiah, D. J. Kereiakes, S. S. Vasudevan, N. Lopes, B. Y. Su, N. A. Flavahan, and P. J. Goldschmidt-Clermont Activated Monocytes Induce Smooth Muscle Cell Death: Role of Macrophage Colony-Stimulating Factor and Cell Contact Circulation, January 15, 2002; 105(2): 174 - 180. [Abstract] [Full Text] [PDF]

				C. B. Forsyth, D. A. Solovjov, T. P. Ugarova, and E. F. Plow Integrin {alpha}M{beta}2-mediated Cell Migration to Fibrinogen and Its Recognition Peptides J. Exp. Med., May 14, 2001; 193(10): 1123 - 1134. [Abstract] [Full Text] [PDF]

				C. Kupatt, H. Habazettl, P. Hanusch, R. Wichels, D. Hahnel, B. F. Becker, and P. Boekstegers c7E3Fab Reduces Postischemic Leukocyte-Thrombocyte Interaction Mediated by Fibrinogen : Implications for Myocardial Reperfusion Injury Arterioscler. Thromb. Vasc. Biol., October 1, 2000; 20(10): 2226 - 2232. [Abstract] [Full Text] [PDF]

				R. D. Thompson, M. W. Wakelin, K. Y. Larbi, A. Dewar, G. Asimakopoulos, M. A. Horton, M. T. Nakada, and S. Nourshargh Divergent Effects of Platelet-Endothelial Cell Adhesion Molecule-1 and {beta}3 Integrin Blockade on Leukocyte Transmigration In Vivo J. Immunol., July 1, 2000; 165(1): 426 - 434. [Abstract] [Full Text] [PDF]

				K. Peter, M. Schwarz, C. Conradt, T. Nordt, M. Moser, W. Kubler, and C. Bode Heparin Inhibits Ligand Binding to the Leukocyte Integrin Mac-1 (CD11b/CD18) Circulation, October 5, 1999; 100(14): 1533 - 1539. [Abstract] [Full Text] [PDF]

				V. P. Yakubenko, D. A. Solovjov, L. Zhang, V. C. Yee, E. F. Plow, and T. P. Ugarova Identification of the Binding Site for Fibrinogen Recognition Peptide gamma 383-395 within the alpha MI-Domain of Integrin alpha Mbeta 2 J. Biol. Chem., April 20, 2001; 276(17): 13995 - 14003. [Abstract] [Full Text] [PDF]