Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury

William J. Janssen, Lea Barthel, Alaina Muldrow, Rebecca E. Oberley-Deegan, Mark T. Kearns, Claudia Jakubzick, Peter M. Henson

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Rationale: During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored. Objectives: To determine the fate of resident and recruited macrophages during the resolution of ALI in mice and to elucidate the mechanisms responsible for macrophage removal. Methods: ALI was induced in mice using influenza A (H1N1; PR8) infection and LPS instillation. Dye labeling techniques, bone marrow transplantation, and surface immunophenotyping were used to distinguish resident and recruited macrophages during inflammation and to study the role of Fas in determining macrophage fate during resolving ALI. Measurements and Main Results: During acute and resolving lung injury from influenza A and LPS, a high proportion of the original resident alveolar macrophages persisted. In contrast, recruited macrophages exhibited robust accumulation in early inflammation, followed by a progressive decline in their number. This decline was mediated by apoptosis with local phagocytic clearance. Recruited macrophages expressed high levels of the death receptor Fas and were rapidly depleted from the airspaces by Fas-activating antibodies. In contrast, macrophage depletion was inhibited in mice treated with Fas-blocking antibodies and in chimeras with Fasdeficient bone marrow. Caspase-8 inhibition preventedmacrophage apoptosis and delayed the resolution of ALI. Conclusions: These findings indicate that Fas-induced apoptosis of recruitedmacrophages is essential for complete resolution of ALI.

Original languageEnglish (US)
Pages (from-to)547-560
Number of pages14
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume184
Issue number5
DOIs
StatePublished - Sep 1 2011

Fingerprint

Acute Lung Injury
Macrophages
Apoptosis
Inflammation
Human Influenza
Immunophenotyping
Death Domain Receptors
Blocking Antibodies
Caspase 8
Alveolar Macrophages
Bone Marrow Transplantation
Monocytes
Coloring Agents
Bone Marrow
Antibodies

Keywords

  • Apoptosis
  • Inflammation
  • Monocyte

ASJC Scopus subject areas

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

Cite this

Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. / Janssen, William J.; Barthel, Lea; Muldrow, Alaina; Oberley-Deegan, Rebecca E.; Kearns, Mark T.; Jakubzick, Claudia; Henson, Peter M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 184, No. 5, 01.09.2011, p. 547-560.

Research output: Contribution to journalArticle

Janssen, William J. ; Barthel, Lea ; Muldrow, Alaina ; Oberley-Deegan, Rebecca E. ; Kearns, Mark T. ; Jakubzick, Claudia ; Henson, Peter M. / Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. In: American Journal of Respiratory and Critical Care Medicine. 2011 ; Vol. 184, No. 5. pp. 547-560.
@article{c024570828fa4287a287a399d9a7b640,
title = "Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury",
abstract = "Rationale: During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored. Objectives: To determine the fate of resident and recruited macrophages during the resolution of ALI in mice and to elucidate the mechanisms responsible for macrophage removal. Methods: ALI was induced in mice using influenza A (H1N1; PR8) infection and LPS instillation. Dye labeling techniques, bone marrow transplantation, and surface immunophenotyping were used to distinguish resident and recruited macrophages during inflammation and to study the role of Fas in determining macrophage fate during resolving ALI. Measurements and Main Results: During acute and resolving lung injury from influenza A and LPS, a high proportion of the original resident alveolar macrophages persisted. In contrast, recruited macrophages exhibited robust accumulation in early inflammation, followed by a progressive decline in their number. This decline was mediated by apoptosis with local phagocytic clearance. Recruited macrophages expressed high levels of the death receptor Fas and were rapidly depleted from the airspaces by Fas-activating antibodies. In contrast, macrophage depletion was inhibited in mice treated with Fas-blocking antibodies and in chimeras with Fasdeficient bone marrow. Caspase-8 inhibition preventedmacrophage apoptosis and delayed the resolution of ALI. Conclusions: These findings indicate that Fas-induced apoptosis of recruitedmacrophages is essential for complete resolution of ALI.",
keywords = "Apoptosis, Inflammation, Monocyte",
author = "Janssen, {William J.} and Lea Barthel and Alaina Muldrow and Oberley-Deegan, {Rebecca E.} and Kearns, {Mark T.} and Claudia Jakubzick and Henson, {Peter M.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1164/rccm.201011-1891OC",
language = "English (US)",
volume = "184",
pages = "547--560",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury

AU - Janssen, William J.

AU - Barthel, Lea

AU - Muldrow, Alaina

AU - Oberley-Deegan, Rebecca E.

AU - Kearns, Mark T.

AU - Jakubzick, Claudia

AU - Henson, Peter M.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Rationale: During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored. Objectives: To determine the fate of resident and recruited macrophages during the resolution of ALI in mice and to elucidate the mechanisms responsible for macrophage removal. Methods: ALI was induced in mice using influenza A (H1N1; PR8) infection and LPS instillation. Dye labeling techniques, bone marrow transplantation, and surface immunophenotyping were used to distinguish resident and recruited macrophages during inflammation and to study the role of Fas in determining macrophage fate during resolving ALI. Measurements and Main Results: During acute and resolving lung injury from influenza A and LPS, a high proportion of the original resident alveolar macrophages persisted. In contrast, recruited macrophages exhibited robust accumulation in early inflammation, followed by a progressive decline in their number. This decline was mediated by apoptosis with local phagocytic clearance. Recruited macrophages expressed high levels of the death receptor Fas and were rapidly depleted from the airspaces by Fas-activating antibodies. In contrast, macrophage depletion was inhibited in mice treated with Fas-blocking antibodies and in chimeras with Fasdeficient bone marrow. Caspase-8 inhibition preventedmacrophage apoptosis and delayed the resolution of ALI. Conclusions: These findings indicate that Fas-induced apoptosis of recruitedmacrophages is essential for complete resolution of ALI.

AB - Rationale: During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored. Objectives: To determine the fate of resident and recruited macrophages during the resolution of ALI in mice and to elucidate the mechanisms responsible for macrophage removal. Methods: ALI was induced in mice using influenza A (H1N1; PR8) infection and LPS instillation. Dye labeling techniques, bone marrow transplantation, and surface immunophenotyping were used to distinguish resident and recruited macrophages during inflammation and to study the role of Fas in determining macrophage fate during resolving ALI. Measurements and Main Results: During acute and resolving lung injury from influenza A and LPS, a high proportion of the original resident alveolar macrophages persisted. In contrast, recruited macrophages exhibited robust accumulation in early inflammation, followed by a progressive decline in their number. This decline was mediated by apoptosis with local phagocytic clearance. Recruited macrophages expressed high levels of the death receptor Fas and were rapidly depleted from the airspaces by Fas-activating antibodies. In contrast, macrophage depletion was inhibited in mice treated with Fas-blocking antibodies and in chimeras with Fasdeficient bone marrow. Caspase-8 inhibition preventedmacrophage apoptosis and delayed the resolution of ALI. Conclusions: These findings indicate that Fas-induced apoptosis of recruitedmacrophages is essential for complete resolution of ALI.

KW - Apoptosis

KW - Inflammation

KW - Monocyte

UR - http://www.scopus.com/inward/record.url?scp=80052472550&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052472550&partnerID=8YFLogxK

U2 - 10.1164/rccm.201011-1891OC

DO - 10.1164/rccm.201011-1891OC

M3 - Article

C2 - 21471090

AN - SCOPUS:80052472550

VL - 184

SP - 547

EP - 560

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -