Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection

Jacob A. Kanter, Haiying Sun, Stephen Chiu, Malcom McAvoy DeCamp Jr, Peter H Sporn, Jacob I Sznajder, Ankit Bharat*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. Methods CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. Results Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P <.0001). CXCL12 enhanced scratch wound closure in both A549 (77.9 ± 0.7% vs 71.5 ± 0.4%; P =.0016) and MLE12 (92.9 ± 4.9% vs 66.0 ± 4.8%; P =.017). CXCL12 enhanced migration by 57% in A549 (P =.0008) and by 86% in MLE12 (P <.0001). AMD3100, a selective CXCR4 antagonist, prevented the effects of CXCL12. CXCL12 increased Rac1 and cofilin activation but did not change bromodeoxyuridine incorporation or cell counts. Conclusion Reduced pleural CXCL12 is associated with PAL. CXCL12 promotes alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation.

Original languageEnglish (US)
Pages (from-to)1073-1082
Number of pages10
JournalSurgery (United States)
Volume158
Issue number4
DOIs
StatePublished - Jan 1 2015

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Alveolar Epithelial Cells
Cell Movement
Actin Depolymerizing Factors
Lung
Air
Wounds and Injuries
Cell Migration Assays
CXCR4 Receptors
Chemokine CXCL12
CXC Chemokines
Bromodeoxyuridine
Wound Healing
Cell Count
Western Blotting
Enzyme-Linked Immunosorbent Assay
Cell Proliferation
Morbidity
Cell Line
Mortality

ASJC Scopus subject areas

  • Surgery

Cite this

@article{b95d9f72742145c8b6dbab7907d2b0b1,
title = "Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection",
abstract = "Background Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. Methods CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. Results Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P <.0001). CXCL12 enhanced scratch wound closure in both A549 (77.9 ± 0.7{\%} vs 71.5 ± 0.4{\%}; P =.0016) and MLE12 (92.9 ± 4.9{\%} vs 66.0 ± 4.8{\%}; P =.017). CXCL12 enhanced migration by 57{\%} in A549 (P =.0008) and by 86{\%} in MLE12 (P <.0001). AMD3100, a selective CXCR4 antagonist, prevented the effects of CXCL12. CXCL12 increased Rac1 and cofilin activation but did not change bromodeoxyuridine incorporation or cell counts. Conclusion Reduced pleural CXCL12 is associated with PAL. CXCL12 promotes alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation.",
author = "Kanter, {Jacob A.} and Haiying Sun and Stephen Chiu and {DeCamp Jr}, {Malcom McAvoy} and Sporn, {Peter H} and Sznajder, {Jacob I} and Ankit Bharat",
year = "2015",
month = "1",
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doi = "10.1016/j.surg.2015.04.051",
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Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection. / Kanter, Jacob A.; Sun, Haiying; Chiu, Stephen; DeCamp Jr, Malcom McAvoy; Sporn, Peter H; Sznajder, Jacob I; Bharat, Ankit.

In: Surgery (United States), Vol. 158, No. 4, 01.01.2015, p. 1073-1082.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection

AU - Kanter, Jacob A.

AU - Sun, Haiying

AU - Chiu, Stephen

AU - DeCamp Jr, Malcom McAvoy

AU - Sporn, Peter H

AU - Sznajder, Jacob I

AU - Bharat, Ankit

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. Methods CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. Results Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P <.0001). CXCL12 enhanced scratch wound closure in both A549 (77.9 ± 0.7% vs 71.5 ± 0.4%; P =.0016) and MLE12 (92.9 ± 4.9% vs 66.0 ± 4.8%; P =.017). CXCL12 enhanced migration by 57% in A549 (P =.0008) and by 86% in MLE12 (P <.0001). AMD3100, a selective CXCR4 antagonist, prevented the effects of CXCL12. CXCL12 increased Rac1 and cofilin activation but did not change bromodeoxyuridine incorporation or cell counts. Conclusion Reduced pleural CXCL12 is associated with PAL. CXCL12 promotes alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation.

AB - Background Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. Methods CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. Results Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P <.0001). CXCL12 enhanced scratch wound closure in both A549 (77.9 ± 0.7% vs 71.5 ± 0.4%; P =.0016) and MLE12 (92.9 ± 4.9% vs 66.0 ± 4.8%; P =.017). CXCL12 enhanced migration by 57% in A549 (P =.0008) and by 86% in MLE12 (P <.0001). AMD3100, a selective CXCR4 antagonist, prevented the effects of CXCL12. CXCL12 increased Rac1 and cofilin activation but did not change bromodeoxyuridine incorporation or cell counts. Conclusion Reduced pleural CXCL12 is associated with PAL. CXCL12 promotes alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation.

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U2 - 10.1016/j.surg.2015.04.051

DO - 10.1016/j.surg.2015.04.051

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JF - Surgery

SN - 0039-6060

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