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 language | English |
|---|---|
| Pages (from-to) | 2273-2281 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 190 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2013 Mar 1 |
Fingerprint
ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
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 -