Integrin αDβ2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties

Valentin P. Yakubenko, Satya P. Yadav, Tatiana P. Ugarova

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Integrin αDβ2, the most recently discovered member of the β2 subfamily of integrin adhesion receptors, is up-regulated on macrophage foam cells. Although other members of the subfamily have been subjects of extensive research, the recognition specificity and the molecular basis for αDβ2 ligand binding remain unknown. Based on the high extent of structural homology between αDβ2 and the major myeloid-cell-specific integrin αMβ2 (Mac-1), noted for its capacity to bind multiple ligands, we considered that the 2 integrins have similar recognition specificity. In this study, using recombinant and natural αDβ2-expressing cells, we demonstrate that αDβ2 supports adhesion and migration to many extracellular matrix proteins in a fashion similar to αMβ 2. Consistent with these data, the recombinant αDI- domain of the receptor bound selected ligands. The binding was activation-dependent because the αDI-domain with its C-terminal α7 helix truncated, but not the form with the C-terminal part extended, bound ligands. When the αDI-domain segment Lys 244-Lys260 (highly homologous to its αMI- domain counterpart Lys245-Arg261 responsible for αMβ2 multiligand-binding properties) was inserted into the monospecific αLI-domain, the chimeric protein bound many ligands with affinities similar to those of wild-type αDI-domain. These results establish integrin αDβ2 as a multiligand receptor and indicate that the mechanism whereby αDβ2 exhibits broad ligand specificity resembles that used by αMβ2, the most promiscuous member of the integrin family.

Original languageEnglish (US)
Pages (from-to)1643-1650
Number of pages8
JournalBlood
Volume107
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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