Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like Macrophage Activity and Disease Severity in COPD

Derek E. Byers, Kangyun Wu, Geoffrey Dang-Vu, Xiaohua Jin, Eugene Agapov, Xiaofeng Zhang, John T. Battaile, Kenneth Schechtman, Roger Yusen, Richard A. Pierce, Michael J. Holtzman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Cell and animal models show a key role for Triggering Receptor Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral infection, but comparable evidence in humans still needs to be established. Methods Lung tissue samples were obtained from lung transplant recipients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n = 16), nontransplantable donor lung tissues (n = 7), and resected lung tissues from patients at risk or with GOLD stage I through IV (n = 55) and were assessed for TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of a type 2 immune response. Results TREM2 (but not TREM1) mRNA levels were increased in GOLD stage IV COPD lung tissues compared with non-COPD lung tissues. TREM2 mRNA was coexpressed with its signaling molecule DAP12 and the macrophage marker CD68 and M2-macrophage markers CD206 and CHIT1. TREM-2 protein was also increased in COPD lung tissues and was localized to CD14+ macrophages by flow cytometry and CD68+ and CCR2+ macrophages by tissue immunostaining. In lung samples from patients at risk and with GOLD stage I through IV COPD, TREM2 but not TREM1 mRNA levels were also increased, and the ratio of TREM2/TREM1 mRNA levels was associated with increases in CHIT1 mRNA and decreases in FEV1 and FEV1/FVC. Conclusions TREM-2 expression is increased in lung macrophages in COPD, particularly in comparison with TREM-1. Therefore, TREM-2 levels and the ratio of TREM-2/TREM-1 signifies M2 activation in COPD lung tissues and may help to guide therapeutics directed against the type 2 immune response in patients with this disease.

Original languageEnglish (US)
Pages (from-to)77-86
Number of pages10
JournalChest
Volume153
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Myeloid Cells
Chronic Obstructive Pulmonary Disease
Macrophages
Lung
Messenger RNA
Virus Diseases
Flow Cytometry
Proteins
Chronic Disease
Animal Models
Tissue Donors

Keywords

  • COPD
  • macrophages
  • translating basic research
  • Triggering Receptor Expressed on Myeloid Cells-2
  • type 2 inflammation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like Macrophage Activity and Disease Severity in COPD. / Byers, Derek E.; Wu, Kangyun; Dang-Vu, Geoffrey; Jin, Xiaohua; Agapov, Eugene; Zhang, Xiaofeng; Battaile, John T.; Schechtman, Kenneth; Yusen, Roger; Pierce, Richard A.; Holtzman, Michael J.

In: Chest, Vol. 153, No. 1, 01.01.2018, p. 77-86.

Research output: Contribution to journalArticle

Byers, DE, Wu, K, Dang-Vu, G, Jin, X, Agapov, E, Zhang, X, Battaile, JT, Schechtman, K, Yusen, R, Pierce, RA & Holtzman, MJ 2018, 'Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like Macrophage Activity and Disease Severity in COPD', Chest, vol. 153, no. 1, pp. 77-86. https://doi.org/10.1016/j.chest.2017.09.044
Byers, Derek E. ; Wu, Kangyun ; Dang-Vu, Geoffrey ; Jin, Xiaohua ; Agapov, Eugene ; Zhang, Xiaofeng ; Battaile, John T. ; Schechtman, Kenneth ; Yusen, Roger ; Pierce, Richard A. ; Holtzman, Michael J. / Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like Macrophage Activity and Disease Severity in COPD. In: Chest. 2018 ; Vol. 153, No. 1. pp. 77-86.
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abstract = "Background Cell and animal models show a key role for Triggering Receptor Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral infection, but comparable evidence in humans still needs to be established. Methods Lung tissue samples were obtained from lung transplant recipients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n = 16), nontransplantable donor lung tissues (n = 7), and resected lung tissues from patients at risk or with GOLD stage I through IV (n = 55) and were assessed for TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of a type 2 immune response. Results TREM2 (but not TREM1) mRNA levels were increased in GOLD stage IV COPD lung tissues compared with non-COPD lung tissues. TREM2 mRNA was coexpressed with its signaling molecule DAP12 and the macrophage marker CD68 and M2-macrophage markers CD206 and CHIT1. TREM-2 protein was also increased in COPD lung tissues and was localized to CD14+ macrophages by flow cytometry and CD68+ and CCR2+ macrophages by tissue immunostaining. In lung samples from patients at risk and with GOLD stage I through IV COPD, TREM2 but not TREM1 mRNA levels were also increased, and the ratio of TREM2/TREM1 mRNA levels was associated with increases in CHIT1 mRNA and decreases in FEV1 and FEV1/FVC. Conclusions TREM-2 expression is increased in lung macrophages in COPD, particularly in comparison with TREM-1. Therefore, TREM-2 levels and the ratio of TREM-2/TREM-1 signifies M2 activation in COPD lung tissues and may help to guide therapeutics directed against the type 2 immune response in patients with this disease.",
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AU - Byers, Derek E.

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AU - Dang-Vu, Geoffrey

AU - Jin, Xiaohua

AU - Agapov, Eugene

AU - Zhang, Xiaofeng

AU - Battaile, John T.

AU - Schechtman, Kenneth

AU - Yusen, Roger

AU - Pierce, Richard A.

AU - Holtzman, Michael J.

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N2 - Background Cell and animal models show a key role for Triggering Receptor Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral infection, but comparable evidence in humans still needs to be established. Methods Lung tissue samples were obtained from lung transplant recipients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n = 16), nontransplantable donor lung tissues (n = 7), and resected lung tissues from patients at risk or with GOLD stage I through IV (n = 55) and were assessed for TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of a type 2 immune response. Results TREM2 (but not TREM1) mRNA levels were increased in GOLD stage IV COPD lung tissues compared with non-COPD lung tissues. TREM2 mRNA was coexpressed with its signaling molecule DAP12 and the macrophage marker CD68 and M2-macrophage markers CD206 and CHIT1. TREM-2 protein was also increased in COPD lung tissues and was localized to CD14+ macrophages by flow cytometry and CD68+ and CCR2+ macrophages by tissue immunostaining. In lung samples from patients at risk and with GOLD stage I through IV COPD, TREM2 but not TREM1 mRNA levels were also increased, and the ratio of TREM2/TREM1 mRNA levels was associated with increases in CHIT1 mRNA and decreases in FEV1 and FEV1/FVC. Conclusions TREM-2 expression is increased in lung macrophages in COPD, particularly in comparison with TREM-1. Therefore, TREM-2 levels and the ratio of TREM-2/TREM-1 signifies M2 activation in COPD lung tissues and may help to guide therapeutics directed against the type 2 immune response in patients with this disease.

AB - Background Cell and animal models show a key role for Triggering Receptor Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral infection, but comparable evidence in humans still needs to be established. Methods Lung tissue samples were obtained from lung transplant recipients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n = 16), nontransplantable donor lung tissues (n = 7), and resected lung tissues from patients at risk or with GOLD stage I through IV (n = 55) and were assessed for TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of a type 2 immune response. Results TREM2 (but not TREM1) mRNA levels were increased in GOLD stage IV COPD lung tissues compared with non-COPD lung tissues. TREM2 mRNA was coexpressed with its signaling molecule DAP12 and the macrophage marker CD68 and M2-macrophage markers CD206 and CHIT1. TREM-2 protein was also increased in COPD lung tissues and was localized to CD14+ macrophages by flow cytometry and CD68+ and CCR2+ macrophages by tissue immunostaining. In lung samples from patients at risk and with GOLD stage I through IV COPD, TREM2 but not TREM1 mRNA levels were also increased, and the ratio of TREM2/TREM1 mRNA levels was associated with increases in CHIT1 mRNA and decreases in FEV1 and FEV1/FVC. Conclusions TREM-2 expression is increased in lung macrophages in COPD, particularly in comparison with TREM-1. Therefore, TREM-2 levels and the ratio of TREM-2/TREM-1 signifies M2 activation in COPD lung tissues and may help to guide therapeutics directed against the type 2 immune response in patients with this disease.

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