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Blood, 1 August 2004, Vol. 104, No. 3, pp. 719-726. Prepublished online as a Blood First Edition Paper on April 13, 2004; DOI 10.1182/blood-2003-09-3016. This Article Full Text (PDF) All Versions of this Article: 2003-09-3016v1 104/3/719    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lishko, V. K Articles by Ugarova, T. P Search for Related Content PubMed PubMed Citation Articles by Lishko, V. K Articles by Ugarova, T. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 3, 2003 Accepted March 24, 2004 Characterization of plasminogen as an adhesive ligand for integrins M2 (Mac-1) and 51(VLA-5) Valeryi K Lishko, Valery V Novokhatny, Valentin P Yakubenko, Helen V Skomorovska-Prokvolit, and Tatiana P Ugarova* Molecular Cardiology, Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, OH, USA Biological Products Division, Bayer HealthCare LLC, Research Triangle Park, NC, USA * Corresponding author; email: ugarovat{at}ccf.org. Plasminogen (Pg) has been implicated in many biological processes involving extracellular proteolysis. We investigated whether Pg, by virtue of its capacity to be deposited within the extracellular matrix, can serve as a ligand for cell surface integrins. We report here that Pg supports cell adhesion by engaging integrins M2 and 51. The immobilized Glu-Pg, but not its derivatives with the N-terminal peptide lacking, plasmin and Lys-Pg, supported efficient adhesion which was abolished by anti-M2 and anti-51 integrin specific mAbs. In addition, lysine-binding sites of Glu-Pg contributed to cell adhesion inasmuch as tranexamic acid and -aminocaproic acid inhibited cell adhesion. The involvement of M2 and 51 in adhesion to Glu-Pg was demonstrable with blood neutrophils, U937 monocytoid cells and genetically engineered M2-transfected HEK 293 cells. In M2, the MI-domain is the binding site for Glu-Pg since the "I-less" form of M2 did not support cell adhesion, and the recombinant MI-domain bound Glu-Pg directly. In comparison with cell adhesion, the binding of soluble Glu-Pg to cells and the concomitant generation of plasmin activity was inhibited by anti-51, but not by anti-M2. These findings identify Glu-Pg as an adhesive ligand for integrins M2 and 51, and suggest that 51 may participate in the binding of soluble Glu-Pg and assist in its activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. K. Lishko, T. Burke, and T. Ugarova Antiadhesive effect of fibrinogen: a safeguard for thrombus stability Blood, February 15, 2007; 109(4): 1541 - 1549. [Abstract] [Full Text] [PDF] V. P. Yakubenko, S. P. Yadav, and T. P. Ugarova Integrin {alpha}Dbeta2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties Blood, February 15, 2006; 107(4): 1643 - 1650. [Abstract] [Full Text] [PDF]

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