Vitronectin Inhibits Efferocytosis Through Interactions with Apoptotic Cells As Well As with Macrophages

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2013 Jan 25

PMID 23345331

Citations 15

Authors

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

Affiliations

Soon will be listed here.

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 LPS-induced 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.

Citing Articles

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