The C-terminus of α2-antiplasmin interacts with endothelial cells

L. Thomas, N. R. Moore, S. Miller, N. A. Booth

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The serpin, α2-antiplasmin (α2AP), has an extended C-terminus relative to other inhibitors. This 51-residue region contains an RGD sequence; such sequences constitute a key recognition sequence for cell adhesion, mediated through integrins. In the present study, this sequence was expressed in Escherichia coli and its binding to endothelial cells and whether binding depends on the RGD sequence was investigated. Binding to the surface of human umbilical vein endothelial cells (HUVEC-C) was observed by flow cytometry and immunohistochemistry. Binding studies on immobilised cells showed specific and RGD-dependent binding of the peptides to HUVEC-C. The binding of the wild-type peptide to the HUVEC-C was significantly higher than that of a mutant peptide, in which RGD was replaced by SAA (P < 0·05, n = 4). Similarly, ethylenediaminetetraacetic acid decreased the binding of the wild-type peptide (P < 0·05, n = 4). The binding was competed out by full-length α2AP, fibronectin and anti-α5β1. This is the first evidence of binding of the C-terminus of α2AP to endothelial cells via its RGD sequence, with most but not all of the binding being integrin-mediated. We speculate that this interaction with α2AP may potentially play a role in the control of cellular fibrinolysis by regulating local plasmin activity on cell surfaces.
Original languageEnglish
Pages (from-to)472-479
Number of pages8
JournalBritish Journal of Haematology
Volume136
Issue number3
Early online date14 Dec 2006
DOIs
Publication statusPublished - Feb 2007

Keywords

  • alpha 2-antiplasmin
  • endothelial cells
  • integrins
  • RGD sequence
  • plasminogen-activator inhibitor-1
  • ALPHA-2-plasmin inhibitor
  • urokinase receptor
  • binding-site
  • human-plasma
  • alpha-2-antiplasmin
  • vitronectin
  • identification
  • fibrinolysis

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