Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

A diverse group of toxicants has been identified that cause injury to the lung including gases (eg, ozone, chlorine), particulates/aerosols (eg, diesel exhaust, fly ash, other combustion products, mustards, nanomaterials, silica, asbestos), chemotherapeutics (eg, bleomycin), and radiation. The pathologic response to these toxicants depends on the dose and duration of exposure and their physical/chemical properties. A common response to pulmonary toxicant exposure is an accumulation of proinflammatory/cytotoxic M1 macrophages at sites of tissue injury, followed by the appearance of anti-inflammatory/wound repair M2 macrophages. It is thought that the outcome of the pathogenic responses to toxicants depends on the balance in the activity of these macrophage subpopulations. Overactivation of either M1 or M2 macrophages leads to injury and disease pathogenesis. Thus, the very same macrophage-derived mediators, released in controlled amounts to destroy injurious materials and pathogens (eg, reactive oxygen species, reactive nitrogen species, proteases, tumor necrosis factor α) and initiate wound repair (eg, transforming growth factor β, connective tissue growth factor, vascular endothelial growth factor), can exacerbate acute lung injury and/or induce chronic disease such as fibrosis, chronic obstructive pulmonary disease, and asthma, when released in excess. This review focuses on the role of macrophage subsets in acute lung injury and chronic fibrosis. Understanding how these pathologies develop following exposure to toxicants, and the contribution of resident and inflammatory macrophages to disease pathogenesis may lead to the development of novel approaches for treating lung diseases.

Original languageEnglish (US)
Pages (from-to)287-301
Number of pages15
JournalToxicological Sciences
Volume168
Issue number2
DOIs
StatePublished - Apr 1 2019

Fingerprint

Pulmonary Fibrosis
Acute Lung Injury
Macrophages
Pulmonary diseases
Wounds and Injuries
Fibrosis
Repair
Coal Ash
Connective Tissue Growth Factor
Vehicle Emissions
Reactive Nitrogen Species
Mustard Plant
Nanostructures
Ozone
Asbestos
Chlorine
Bleomycin
Lung Injury
Transforming Growth Factors
Pathology

All Science Journal Classification (ASJC) codes

  • Toxicology

Keywords

  • Macrophages
  • cytokines
  • fibrosis
  • inflammatory mediators
  • lung injury
  • oxidants

Cite this

@article{e9f029338b3442c285b1edb167a66f5f,
title = "Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants",
abstract = "A diverse group of toxicants has been identified that cause injury to the lung including gases (eg, ozone, chlorine), particulates/aerosols (eg, diesel exhaust, fly ash, other combustion products, mustards, nanomaterials, silica, asbestos), chemotherapeutics (eg, bleomycin), and radiation. The pathologic response to these toxicants depends on the dose and duration of exposure and their physical/chemical properties. A common response to pulmonary toxicant exposure is an accumulation of proinflammatory/cytotoxic M1 macrophages at sites of tissue injury, followed by the appearance of anti-inflammatory/wound repair M2 macrophages. It is thought that the outcome of the pathogenic responses to toxicants depends on the balance in the activity of these macrophage subpopulations. Overactivation of either M1 or M2 macrophages leads to injury and disease pathogenesis. Thus, the very same macrophage-derived mediators, released in controlled amounts to destroy injurious materials and pathogens (eg, reactive oxygen species, reactive nitrogen species, proteases, tumor necrosis factor α) and initiate wound repair (eg, transforming growth factor β, connective tissue growth factor, vascular endothelial growth factor), can exacerbate acute lung injury and/or induce chronic disease such as fibrosis, chronic obstructive pulmonary disease, and asthma, when released in excess. This review focuses on the role of macrophage subsets in acute lung injury and chronic fibrosis. Understanding how these pathologies develop following exposure to toxicants, and the contribution of resident and inflammatory macrophages to disease pathogenesis may lead to the development of novel approaches for treating lung diseases.",
keywords = "Macrophages, cytokines, fibrosis, inflammatory mediators, lung injury, oxidants",
author = "Laskin, {Debra L.} and Rama Malaviya and Laskin, {Jeffrey D.}",
year = "2019",
month = "4",
day = "1",
doi = "10.1093/toxsci/kfy309",
language = "English (US)",
volume = "168",
pages = "287--301",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants. / Laskin, Debra L.; Malaviya, Rama; Laskin, Jeffrey D.

In: Toxicological Sciences, Vol. 168, No. 2, 01.04.2019, p. 287-301.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants

AU - Laskin, Debra L.

AU - Malaviya, Rama

AU - Laskin, Jeffrey D.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - A diverse group of toxicants has been identified that cause injury to the lung including gases (eg, ozone, chlorine), particulates/aerosols (eg, diesel exhaust, fly ash, other combustion products, mustards, nanomaterials, silica, asbestos), chemotherapeutics (eg, bleomycin), and radiation. The pathologic response to these toxicants depends on the dose and duration of exposure and their physical/chemical properties. A common response to pulmonary toxicant exposure is an accumulation of proinflammatory/cytotoxic M1 macrophages at sites of tissue injury, followed by the appearance of anti-inflammatory/wound repair M2 macrophages. It is thought that the outcome of the pathogenic responses to toxicants depends on the balance in the activity of these macrophage subpopulations. Overactivation of either M1 or M2 macrophages leads to injury and disease pathogenesis. Thus, the very same macrophage-derived mediators, released in controlled amounts to destroy injurious materials and pathogens (eg, reactive oxygen species, reactive nitrogen species, proteases, tumor necrosis factor α) and initiate wound repair (eg, transforming growth factor β, connective tissue growth factor, vascular endothelial growth factor), can exacerbate acute lung injury and/or induce chronic disease such as fibrosis, chronic obstructive pulmonary disease, and asthma, when released in excess. This review focuses on the role of macrophage subsets in acute lung injury and chronic fibrosis. Understanding how these pathologies develop following exposure to toxicants, and the contribution of resident and inflammatory macrophages to disease pathogenesis may lead to the development of novel approaches for treating lung diseases.

AB - A diverse group of toxicants has been identified that cause injury to the lung including gases (eg, ozone, chlorine), particulates/aerosols (eg, diesel exhaust, fly ash, other combustion products, mustards, nanomaterials, silica, asbestos), chemotherapeutics (eg, bleomycin), and radiation. The pathologic response to these toxicants depends on the dose and duration of exposure and their physical/chemical properties. A common response to pulmonary toxicant exposure is an accumulation of proinflammatory/cytotoxic M1 macrophages at sites of tissue injury, followed by the appearance of anti-inflammatory/wound repair M2 macrophages. It is thought that the outcome of the pathogenic responses to toxicants depends on the balance in the activity of these macrophage subpopulations. Overactivation of either M1 or M2 macrophages leads to injury and disease pathogenesis. Thus, the very same macrophage-derived mediators, released in controlled amounts to destroy injurious materials and pathogens (eg, reactive oxygen species, reactive nitrogen species, proteases, tumor necrosis factor α) and initiate wound repair (eg, transforming growth factor β, connective tissue growth factor, vascular endothelial growth factor), can exacerbate acute lung injury and/or induce chronic disease such as fibrosis, chronic obstructive pulmonary disease, and asthma, when released in excess. This review focuses on the role of macrophage subsets in acute lung injury and chronic fibrosis. Understanding how these pathologies develop following exposure to toxicants, and the contribution of resident and inflammatory macrophages to disease pathogenesis may lead to the development of novel approaches for treating lung diseases.

KW - Macrophages

KW - cytokines

KW - fibrosis

KW - inflammatory mediators

KW - lung injury

KW - oxidants

UR - http://www.scopus.com/inward/record.url?scp=85063712089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063712089&partnerID=8YFLogxK

U2 - 10.1093/toxsci/kfy309

DO - 10.1093/toxsci/kfy309

M3 - Review article

C2 - 30590802

AN - SCOPUS:85063712089

VL - 168

SP - 287

EP - 301

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -