Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages

Hong Beom Bae, Jean Marc Tadie, Shaoning Jiang, Dae Won Park, Celeste P. Bell, Lawrence C. Thompson, Cynthia B. Peterson, Victor J. Thannickal, Edward Abraham, Jaroslaw W. Zmijewski

    Research output: Contribution to journalArticlepeer-review

    21 Citations (Scopus)

    Abstract

    Effective removal of apoptotic cells, particularly apoptotic neutrophils, is essential for the successful resolution of acute inflammatory conditions. In these experiments, we found that whereas interaction between vitronectin and integrins diminished the ability of macrophages to ingest apoptotic cells, interaction between vitronectin with urokinase-type plasminogen activator receptor (uPAR) on the surface of apoptotic cells also had equally important inhibitory effects on efferocytosis. Preincubation of vitronectin with plasminogen activator inhibitor-1 eliminated its ability to inhibit phagocytosis of apoptotic cells. Similarly, incubation of apoptotic cells with soluble uPAR or Abs to uPAR significantly diminished efferocytosis. In the setting of LPSinduced ALI, enhanced efferocytosis and decreased numbers of neutrophils were found in bronchoalveolar lavage obtained from vitronectin-deficient (vtn -/-) mice compared with wild type (vtn+/+) mice. Furthermore, there was increased clearance of apoptotic vtn-/- as compared with vtn+/+ neutrophils after introduction into the lungs of vtn-/- mice. Incubation of apoptotic vtn-/- neutrophils with purified vitronectin before intratracheal instillation decreased efferocytosis in vivo. These findings demonstrate that the inhibitory effects of vitronectin on efferocytosis involve interactions with both the engulfing phagocyte and the apoptotic target cell.

    Original languageEnglish
    Pages (from-to)2273-2281
    Number of pages9
    JournalJournal of Immunology
    Volume190
    Issue number5
    DOIs
    Publication statusPublished - 2013 Mar 1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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