Macrophages and polymorphonuclear neutrophils in lung defense and injury

Y. Sibille, Herbert Reynolds

Research output: Contribution to journalReview article

881 Citations (Scopus)

Abstract

Phagocytes, in particular macrophages and PMN, are now recognized as major components of inflammatory and immunologic reactions in the lung. Normally, macrophages represent the majority of phagocytes in the lower respiratory tract. These lung macrophages are morphologically and functionally heterogenous and include alveolar, interstitial, intravascular, and airway macrophages, each with characteristic morphologic and functional features. Through the presence of surface receptors for numerous ligands and through their large number of secretory products, lung macrophages can respond to environmental factors and account for most of the clearance of microparticles and microorganisms in the distal airways and the alveolar spaces. In addition, macrophages also play an important role in inflammatory processes through the release of oxygen radicals and proteolytic enzymes. Through the release of several cytokines, i.e., growth-promoting and inhibiting factors, lung macrophages may also influence both matrix damage and repair processes. Macrophages can also contribute to the alveolitis by recruitment of inflammatory and immune cells. This latter contribution is best demonstrated in migration movement of PMN. The normal distal airways generally contain a small number of PMN, but the pulmonary vascular bed represents a large reservoir of PMN. Some of them are in intimate contact with the endothelium, forming the so-called marginating pool of PMN. Because the capillary lumen is separated only from the alveolar space by a monolayer of endothelial and epithelial cells on each side of a thin interstitial matrix, it is likely that some inhibitory mechanism exists to prevent PMN from migrating towards the alveolar space. Such inhibitors of PMN migration are present both in serum and in the alveolar space, some being released by alveolar macrophages. However, alveolar macrophages can also secrete factors called chemotaxins that attract PMN to the airways, and this supports a central role for alveolar macrophages in the regulation of PMN traffic in the lungs. Thus, secretory products of alveolar macrophages are part of the regulatory mechanisms of PMN mobility and adherence that appears to be crucial in the initiation of some inflammatory reactions. The contribution of phagocytes to the defense against infection and tumor has been documented mostly in vitro. Thus, both oxygen radicals, in particular hydroxyl radicals and proteases such as lysozyme, are potent bactericidal agents. That phagocytes are also important defenders of the lungs in vivo is best supported by the observations in immunodeficient patients and animal models. Patients with leukopenia and animals may suffer life-threatening infections often involving the lungs. Also, specific defects in phagocyte functions such as in chronic granulomatous disease (lack of oxidative burst) or in alveolar proteinosis (impaired phagocytosis by macrophages) are associated with severe infectious problems. In addition to their major defensive role, phagocytes occasionally can be associated with injurious processes, especially in the lung, and this appears to result from an inadequate or unrestrained activation of either macrophages or PMN or both. Again, this is mostly substantiated by in vitro studies. However, studies in emphysema and in idiopathic pulmonary fibrosis suggest that oxidants and proteases (including elastase) derived from PMN and probably from alveolar macrophages contribute in vivo to lung matrix degradation. In conclusion, alveolar macrophages and PMN participate in both defense and injury processes of the lungs. As the resident phagocyte of the lower respiratory tract, the macrophage is a versatile cell with paradoxical effects, able to release oxidants, proteolytic enzymes, and mediators, but also able to secrete antioxidants, antiproteases, and inhibitors of cytokines. By contrast, the PMN is virtually absent from the alveoli (approximately 1% of normal, nonsmoker bronchoalveolar cells). However, when recruited in inflammatory states, PMN can outnumber macrophages and release substantial amounts of oxygen species and enzymes. Hence, phagocytes represent only one component of a complex network of cellular and humoral factors interacting in defense, injury, and immune reaction. Lymphocytes, platelets, eosinophils, fibroblasts, epithelial and endothelial cells are also implicated in lung injury and repair, either independently or synergistically with macrophages and/or PMN. In particular, through the release of lymphokines, lymphocytes appear to play a central role in the regulation of both macrophages and PMN function in interstitial lung diseases. This role may vary considerably depending on the triggering agent(s), unknown in most cases.

Original languageEnglish (US)
Pages (from-to)471-501
Number of pages31
JournalAmerican Review of Respiratory Disease
Volume141
Issue number2 I
DOIs
StatePublished - Jan 1 1990

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Lung Injury
Neutrophils
Macrophages
Phagocytes
Alveolar Macrophages
Lung
Peptide Hydrolases
Oxidants
Respiratory System
Reactive Oxygen Species
Endothelial Cells
Epithelial Cells
Lymphocytes
Cytokines
Chronic Granulomatous Disease
Idiopathic Pulmonary Fibrosis
Leukocyte Elastase
Respiratory Burst
Macrophage Activation
Lymphokines

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Sibille, Y. ; Reynolds, Herbert. / Macrophages and polymorphonuclear neutrophils in lung defense and injury. In: American Review of Respiratory Disease. 1990 ; Vol. 141, No. 2 I. pp. 471-501.
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abstract = "Phagocytes, in particular macrophages and PMN, are now recognized as major components of inflammatory and immunologic reactions in the lung. Normally, macrophages represent the majority of phagocytes in the lower respiratory tract. These lung macrophages are morphologically and functionally heterogenous and include alveolar, interstitial, intravascular, and airway macrophages, each with characteristic morphologic and functional features. Through the presence of surface receptors for numerous ligands and through their large number of secretory products, lung macrophages can respond to environmental factors and account for most of the clearance of microparticles and microorganisms in the distal airways and the alveolar spaces. In addition, macrophages also play an important role in inflammatory processes through the release of oxygen radicals and proteolytic enzymes. Through the release of several cytokines, i.e., growth-promoting and inhibiting factors, lung macrophages may also influence both matrix damage and repair processes. Macrophages can also contribute to the alveolitis by recruitment of inflammatory and immune cells. This latter contribution is best demonstrated in migration movement of PMN. The normal distal airways generally contain a small number of PMN, but the pulmonary vascular bed represents a large reservoir of PMN. Some of them are in intimate contact with the endothelium, forming the so-called marginating pool of PMN. Because the capillary lumen is separated only from the alveolar space by a monolayer of endothelial and epithelial cells on each side of a thin interstitial matrix, it is likely that some inhibitory mechanism exists to prevent PMN from migrating towards the alveolar space. Such inhibitors of PMN migration are present both in serum and in the alveolar space, some being released by alveolar macrophages. However, alveolar macrophages can also secrete factors called chemotaxins that attract PMN to the airways, and this supports a central role for alveolar macrophages in the regulation of PMN traffic in the lungs. Thus, secretory products of alveolar macrophages are part of the regulatory mechanisms of PMN mobility and adherence that appears to be crucial in the initiation of some inflammatory reactions. The contribution of phagocytes to the defense against infection and tumor has been documented mostly in vitro. Thus, both oxygen radicals, in particular hydroxyl radicals and proteases such as lysozyme, are potent bactericidal agents. That phagocytes are also important defenders of the lungs in vivo is best supported by the observations in immunodeficient patients and animal models. Patients with leukopenia and animals may suffer life-threatening infections often involving the lungs. Also, specific defects in phagocyte functions such as in chronic granulomatous disease (lack of oxidative burst) or in alveolar proteinosis (impaired phagocytosis by macrophages) are associated with severe infectious problems. In addition to their major defensive role, phagocytes occasionally can be associated with injurious processes, especially in the lung, and this appears to result from an inadequate or unrestrained activation of either macrophages or PMN or both. Again, this is mostly substantiated by in vitro studies. However, studies in emphysema and in idiopathic pulmonary fibrosis suggest that oxidants and proteases (including elastase) derived from PMN and probably from alveolar macrophages contribute in vivo to lung matrix degradation. In conclusion, alveolar macrophages and PMN participate in both defense and injury processes of the lungs. As the resident phagocyte of the lower respiratory tract, the macrophage is a versatile cell with paradoxical effects, able to release oxidants, proteolytic enzymes, and mediators, but also able to secrete antioxidants, antiproteases, and inhibitors of cytokines. By contrast, the PMN is virtually absent from the alveoli (approximately 1{\%} of normal, nonsmoker bronchoalveolar cells). However, when recruited in inflammatory states, PMN can outnumber macrophages and release substantial amounts of oxygen species and enzymes. Hence, phagocytes represent only one component of a complex network of cellular and humoral factors interacting in defense, injury, and immune reaction. Lymphocytes, platelets, eosinophils, fibroblasts, epithelial and endothelial cells are also implicated in lung injury and repair, either independently or synergistically with macrophages and/or PMN. In particular, through the release of lymphokines, lymphocytes appear to play a central role in the regulation of both macrophages and PMN function in interstitial lung diseases. This role may vary considerably depending on the triggering agent(s), unknown in most cases.",
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Macrophages and polymorphonuclear neutrophils in lung defense and injury. / Sibille, Y.; Reynolds, Herbert.

In: American Review of Respiratory Disease, Vol. 141, No. 2 I, 01.01.1990, p. 471-501.

Research output: Contribution to journalReview article

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AU - Reynolds, Herbert

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N2 - Phagocytes, in particular macrophages and PMN, are now recognized as major components of inflammatory and immunologic reactions in the lung. Normally, macrophages represent the majority of phagocytes in the lower respiratory tract. These lung macrophages are morphologically and functionally heterogenous and include alveolar, interstitial, intravascular, and airway macrophages, each with characteristic morphologic and functional features. Through the presence of surface receptors for numerous ligands and through their large number of secretory products, lung macrophages can respond to environmental factors and account for most of the clearance of microparticles and microorganisms in the distal airways and the alveolar spaces. In addition, macrophages also play an important role in inflammatory processes through the release of oxygen radicals and proteolytic enzymes. Through the release of several cytokines, i.e., growth-promoting and inhibiting factors, lung macrophages may also influence both matrix damage and repair processes. Macrophages can also contribute to the alveolitis by recruitment of inflammatory and immune cells. This latter contribution is best demonstrated in migration movement of PMN. The normal distal airways generally contain a small number of PMN, but the pulmonary vascular bed represents a large reservoir of PMN. Some of them are in intimate contact with the endothelium, forming the so-called marginating pool of PMN. Because the capillary lumen is separated only from the alveolar space by a monolayer of endothelial and epithelial cells on each side of a thin interstitial matrix, it is likely that some inhibitory mechanism exists to prevent PMN from migrating towards the alveolar space. Such inhibitors of PMN migration are present both in serum and in the alveolar space, some being released by alveolar macrophages. However, alveolar macrophages can also secrete factors called chemotaxins that attract PMN to the airways, and this supports a central role for alveolar macrophages in the regulation of PMN traffic in the lungs. Thus, secretory products of alveolar macrophages are part of the regulatory mechanisms of PMN mobility and adherence that appears to be crucial in the initiation of some inflammatory reactions. The contribution of phagocytes to the defense against infection and tumor has been documented mostly in vitro. Thus, both oxygen radicals, in particular hydroxyl radicals and proteases such as lysozyme, are potent bactericidal agents. That phagocytes are also important defenders of the lungs in vivo is best supported by the observations in immunodeficient patients and animal models. Patients with leukopenia and animals may suffer life-threatening infections often involving the lungs. Also, specific defects in phagocyte functions such as in chronic granulomatous disease (lack of oxidative burst) or in alveolar proteinosis (impaired phagocytosis by macrophages) are associated with severe infectious problems. In addition to their major defensive role, phagocytes occasionally can be associated with injurious processes, especially in the lung, and this appears to result from an inadequate or unrestrained activation of either macrophages or PMN or both. Again, this is mostly substantiated by in vitro studies. However, studies in emphysema and in idiopathic pulmonary fibrosis suggest that oxidants and proteases (including elastase) derived from PMN and probably from alveolar macrophages contribute in vivo to lung matrix degradation. In conclusion, alveolar macrophages and PMN participate in both defense and injury processes of the lungs. As the resident phagocyte of the lower respiratory tract, the macrophage is a versatile cell with paradoxical effects, able to release oxidants, proteolytic enzymes, and mediators, but also able to secrete antioxidants, antiproteases, and inhibitors of cytokines. By contrast, the PMN is virtually absent from the alveoli (approximately 1% of normal, nonsmoker bronchoalveolar cells). However, when recruited in inflammatory states, PMN can outnumber macrophages and release substantial amounts of oxygen species and enzymes. Hence, phagocytes represent only one component of a complex network of cellular and humoral factors interacting in defense, injury, and immune reaction. Lymphocytes, platelets, eosinophils, fibroblasts, epithelial and endothelial cells are also implicated in lung injury and repair, either independently or synergistically with macrophages and/or PMN. In particular, through the release of lymphokines, lymphocytes appear to play a central role in the regulation of both macrophages and PMN function in interstitial lung diseases. This role may vary considerably depending on the triggering agent(s), unknown in most cases.

AB - Phagocytes, in particular macrophages and PMN, are now recognized as major components of inflammatory and immunologic reactions in the lung. Normally, macrophages represent the majority of phagocytes in the lower respiratory tract. These lung macrophages are morphologically and functionally heterogenous and include alveolar, interstitial, intravascular, and airway macrophages, each with characteristic morphologic and functional features. Through the presence of surface receptors for numerous ligands and through their large number of secretory products, lung macrophages can respond to environmental factors and account for most of the clearance of microparticles and microorganisms in the distal airways and the alveolar spaces. In addition, macrophages also play an important role in inflammatory processes through the release of oxygen radicals and proteolytic enzymes. Through the release of several cytokines, i.e., growth-promoting and inhibiting factors, lung macrophages may also influence both matrix damage and repair processes. Macrophages can also contribute to the alveolitis by recruitment of inflammatory and immune cells. This latter contribution is best demonstrated in migration movement of PMN. The normal distal airways generally contain a small number of PMN, but the pulmonary vascular bed represents a large reservoir of PMN. Some of them are in intimate contact with the endothelium, forming the so-called marginating pool of PMN. Because the capillary lumen is separated only from the alveolar space by a monolayer of endothelial and epithelial cells on each side of a thin interstitial matrix, it is likely that some inhibitory mechanism exists to prevent PMN from migrating towards the alveolar space. Such inhibitors of PMN migration are present both in serum and in the alveolar space, some being released by alveolar macrophages. However, alveolar macrophages can also secrete factors called chemotaxins that attract PMN to the airways, and this supports a central role for alveolar macrophages in the regulation of PMN traffic in the lungs. Thus, secretory products of alveolar macrophages are part of the regulatory mechanisms of PMN mobility and adherence that appears to be crucial in the initiation of some inflammatory reactions. The contribution of phagocytes to the defense against infection and tumor has been documented mostly in vitro. Thus, both oxygen radicals, in particular hydroxyl radicals and proteases such as lysozyme, are potent bactericidal agents. That phagocytes are also important defenders of the lungs in vivo is best supported by the observations in immunodeficient patients and animal models. Patients with leukopenia and animals may suffer life-threatening infections often involving the lungs. Also, specific defects in phagocyte functions such as in chronic granulomatous disease (lack of oxidative burst) or in alveolar proteinosis (impaired phagocytosis by macrophages) are associated with severe infectious problems. In addition to their major defensive role, phagocytes occasionally can be associated with injurious processes, especially in the lung, and this appears to result from an inadequate or unrestrained activation of either macrophages or PMN or both. Again, this is mostly substantiated by in vitro studies. However, studies in emphysema and in idiopathic pulmonary fibrosis suggest that oxidants and proteases (including elastase) derived from PMN and probably from alveolar macrophages contribute in vivo to lung matrix degradation. In conclusion, alveolar macrophages and PMN participate in both defense and injury processes of the lungs. As the resident phagocyte of the lower respiratory tract, the macrophage is a versatile cell with paradoxical effects, able to release oxidants, proteolytic enzymes, and mediators, but also able to secrete antioxidants, antiproteases, and inhibitors of cytokines. By contrast, the PMN is virtually absent from the alveoli (approximately 1% of normal, nonsmoker bronchoalveolar cells). However, when recruited in inflammatory states, PMN can outnumber macrophages and release substantial amounts of oxygen species and enzymes. Hence, phagocytes represent only one component of a complex network of cellular and humoral factors interacting in defense, injury, and immune reaction. Lymphocytes, platelets, eosinophils, fibroblasts, epithelial and endothelial cells are also implicated in lung injury and repair, either independently or synergistically with macrophages and/or PMN. In particular, through the release of lymphokines, lymphocytes appear to play a central role in the regulation of both macrophages and PMN function in interstitial lung diseases. This role may vary considerably depending on the triggering agent(s), unknown in most cases.

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