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 journalArticle

18 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

Fingerprint

Vitronectin
Macrophages
Urokinase Plasminogen Activator Receptors
Neutrophils
Cytophagocytosis
Plasminogen Activator Inhibitor 1
Bronchoalveolar Lavage
Phagocytes
Integrins
Cell Communication
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Bae, H. B., Tadie, J. M., Jiang, S., Park, D. W., Bell, C. P., Thompson, L. C., ... Zmijewski, J. W. (2013). Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages. Journal of Immunology, 190(5), 2273-2281. https://doi.org/10.4049/jimmunol.1200625

Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages. / Bae, Hong Beom; Tadie, Jean Marc; Jiang, Shaoning; Park, Dae Won; Bell, Celeste P.; Thompson, Lawrence C.; Peterson, Cynthia B.; Thannickal, Victor J.; Abraham, Edward; Zmijewski, Jaroslaw W.

In: Journal of Immunology, Vol. 190, No. 5, 01.03.2013, p. 2273-2281.

Research output: Contribution to journalArticle

Bae, HB, Tadie, JM, Jiang, S, Park, DW, Bell, CP, Thompson, LC, Peterson, CB, Thannickal, VJ, Abraham, E & Zmijewski, JW 2013, 'Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages', Journal of Immunology, vol. 190, no. 5, pp. 2273-2281. https://doi.org/10.4049/jimmunol.1200625
Bae, Hong Beom ; Tadie, Jean Marc ; Jiang, Shaoning ; Park, Dae Won ; Bell, Celeste P. ; Thompson, Lawrence C. ; Peterson, Cynthia B. ; Thannickal, Victor J. ; Abraham, Edward ; Zmijewski, Jaroslaw W. / Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages. In: Journal of Immunology. 2013 ; Vol. 190, No. 5. pp. 2273-2281.
@article{f706a265099d4ef0bf5d779a6ccb08b6,
title = "Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages",
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.",
author = "Bae, {Hong Beom} and Tadie, {Jean Marc} and Shaoning Jiang and Park, {Dae Won} and Bell, {Celeste P.} and Thompson, {Lawrence C.} and Peterson, {Cynthia B.} and Thannickal, {Victor J.} and Edward Abraham and Zmijewski, {Jaroslaw W.}",
year = "2013",
month = "3",
day = "1",
doi = "10.4049/jimmunol.1200625",
language = "English",
volume = "190",
pages = "2273--2281",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages

AU - Bae, Hong Beom

AU - Tadie, Jean Marc

AU - Jiang, Shaoning

AU - Park, Dae Won

AU - Bell, Celeste P.

AU - Thompson, Lawrence C.

AU - Peterson, Cynthia B.

AU - Thannickal, Victor J.

AU - Abraham, Edward

AU - Zmijewski, Jaroslaw W.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84874241522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874241522&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1200625

DO - 10.4049/jimmunol.1200625

M3 - Article

VL - 190

SP - 2273

EP - 2281

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -