Affinity modulation of the αIIbβ3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor

Timothy E. O'Toole, Joseph C. Loftus, Xiaoping Du, Alison A. Glass, Zaverio M. Ruggeri, Sanford J. Shattil, Edward F. Plow, Mark H. Ginsberg

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219 Scopus citations

Abstract

To analyze the basis of affinity modulation of integrin function, we studied cloned stable Chinese hamster ovary cell lines expressing recombinant integrins of the β3 family (αIIbβ3 and αvβ3). Antigenic and peptide recognition specificities of the recombinant receptors resembled those of the native receptors found in platelets or endothelial cells. The αIIbβ3-expressing cell line (A5) bound RGD peptides and immobilized fibrinogen (Fg) but not soluble fibrinogen or the activation-specific monoclonal anti-αIIbβ3 (PAC1), indicating that it was in the affinity state found on resting platelets. Several platelet agonists failed to alter the affinity state of ("activate") recombinant αIIbβ3. The binding of soluble Fg and PAC1, however, was stimulated in both platelets and A5 cells by addition of IgG papain-digestion products (Fab) fragments of certain β3-specific monoclonal antibodies. These antibodies stimulated PAC1 binding to platelets fixed under conditions rendering them unresponsive to other agonists. Addition of these antibodies to detergent-solubilized αIIbβ3 also stimulated specific Fg binding. These data demonstrate that certain anti-β3 antibodies activate αIIbβ3 by acting directly on the receptor, possibly by altering its conformation. Furthermore, they indicate that the activation state of αIIbβ3 is a property of the receptor itself rather than of the surrounding cell membrane microenvironment.

Original languageEnglish (US)
Pages (from-to)883-893
Number of pages11
JournalMolecular biology of the cell
Volume1
Issue number12
DOIs
StatePublished - Nov 1990

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    O'Toole, T. E., Loftus, J. C., Du, X., Glass, A. A., Ruggeri, Z. M., Shattil, S. J., Plow, E. F., & Ginsberg, M. H. (1990). Affinity modulation of the αIIbβ3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor. Molecular biology of the cell, 1(12), 883-893. https://doi.org/10.1091/mbc.1.12.883