Characterization of plasminogen as an adhesive ligand for integrins αMβ2 (Mac-1) and α5β 1

Valeryi K. Lishko, Valery V. Novokhatny, Valentin P. Yakubenko, Helen V. Skomorovska-Prokvolit, Tatiana P. Ugarova

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Plasminogen (Pg) has been implicated in many biologic 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 αMβ2 and α5β 1. The immobilized Glu-Pg, but not its derivatives with the N-terminal peptide lacking, plasmin and Lys-Pg, supported efficient adhesion that was abolished by anti-αMβ2 and anti-α5β1 integrin-specific monoclonal antibodies (mAbs). In addition, lysine binding sites of Glu-Pg contributed to cell adhesion inasmuch as tranexamic acid and ε-aminocaproic acid inhibited cell adhesion. The involvement of αMβ2 and α5β1 in adhesion to Glu-Pg was demonstrable with blood neutrophils, U937 monocytoid cells, and genetically engineered αMβ2-transfected human embryonic kidney (HEK) 293 cells. In αMβ2, the αMI- domain is the binding site for Glu-Pg because the "l-less" form of αMβ2 did not support cell adhesion and the recombinant αMI-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- α5β1 but not by anti- αMβ2. These findings identify Glu-Pg as an adhesive ligand for integrins αMβ2 and α5β1 and suggest that α5β 1 may participate in the binding of soluble Glu-Pg and assist in its activation.

Original languageEnglish (US)
Pages (from-to)719-726
Number of pages8
JournalBlood
Volume104
Issue number3
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Lishko, V. K., Novokhatny, V. V., Yakubenko, V. P., Skomorovska-Prokvolit, H. V., & Ugarova, T. P. (2004). Characterization of plasminogen as an adhesive ligand for integrins αMβ2 (Mac-1) and α5β 1. Blood, 104(3), 719-726. https://doi.org/10.1182/blood-2003-09-3016