The role of alveolar macrophages in surfactant turnover

Eckert, H; Lux, Marie; Lachmann, Burkhard

doi:10.1007/bf02713866

Cited by 28 publications

(3 citation statements)

References 13 publications

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“…The Mac III cluster uniquely expressed alveolar macrophage signature genes ( Car4, Bhlhe41, Trim29 ) ( Figure 4A , Table 3 ). Top pathways included the inflammatory response ( Figure 4—figure supplement 1 ), including numerous genes that constrain inflammation ( Cd200r4, Gpnmb, Il1rn ) ( Ripoll et al, 2007 ; Zhang et al, 2004 ), and lipid catabolic processes, including the genes Lpl, Lipa, and Abcg1, indicative of their essential role in surfactant catabolism ( Eckert et al, 1983 ; Baker et al, 2010 ). Tissue remodeling was also identified as a top pathway, including Ctsk , a cysteine protease important for the maintenance of airway structural integrity ( Zhang et al, 2011 ), Serpine1 , a serine protease that can either inhibit ( Wu et al, 2015 ) or promote angiogenesis ( Bajou et al, 2014 ), and Il18 , a pro-inflammatory cytokine that drives both pulmonary vascular and parenchymal remodeling ( Rodriguez-Menocal et al, 2014 ; Kang et al, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution

Domingo-Gonzalez

Zanini

Che

et al. 2020

eLife

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At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Although many studies have focused on the adult lung, the perinatal lung remains unexplored. Here, we present an atlas of the murine lung immune compartment during early postnatal development. We show that the late embryonic lung is dominated by specialized proliferative macrophages with a surprising physical interaction with the developing vasculature. These macrophages disappear after birth and are replaced by a dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed an orchestration of distinct subpopulations across postnatal development to fill context-specific functions in tissue remodeling, angiogenesis, and immunity. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter immune cell phenotype during a period of rapid lung growth and heightened vulnerability.

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Section: Resultsmentioning

confidence: 99%

Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution

Domingo-Gonzalez

Zanini

Che

et al. 2020

eLife

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“…Unilamellar vesicles of ‘spent’ or inactive surfactant are found in the hypophase of the alveolar lining layer (Ochs, ) and are either taken up and recycled or degraded by ATII cells or taken up and degraded by macrophages (Christmann et al ., ; Zuo et al ., ). Thus, macrophages play a role in surfactant homeostasis, the importance of which has been demonstrated by increased surfactant pool in macrophage‐depleted lungs (Forbes et al ., ), by the induction of a foamy macrophage reaction following intraperitoneal administration of known surfactant secretagogues, such as Ambroxol (Eckert et al ., ), and following the administration of exogenous surfactant (Kramer et al ., ). In addition, it is well known that in other conditions of surfactant excess, such as phospholipidosis, there are increased numbers of foamy macrophages and hyperplastic ATII cells (Lewis and McKevitt, ).…”

Section: Aetiologiesmentioning

confidence: 99%

Foamy macrophage responses in the rat lung following exposure to inhaled pharmaceuticals: a simple, pragmatic approach for inhaled drug development

Lewis

Williams

Beck

2013

J of Applied Toxicology

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Successes in the field of respiratory medicines are largely limited to three main target classes: β2 -adrenergic receptor agonists, muscarinic antagonists and corticosteroids. A significant factor in attrition during the development of respiratory medicines is the induction of foamy macrophage responses, particularly, in rats. The term foamy macrophage describes a vacuolated cytoplasmic appearance, seen by light microscopy, which is ultrastructurally characterized by the presence of lysosomal lamellar bodies, neutral lipid droplets or drug particles. We propose a simple classification, based light-heartedly on the theme 'the good, the bad and the ugly', which allows important distinctions to be made between phenotypes, aetiologies and adversity. Foamy macrophages induced in rat lungs by exposure to inhaled β2 -agonists, antimuscarinics and corticosteroids are simple aggregates of uniform cells without other associated pathologies. In contrast, macrophage reactions induced by some other inhaled drug classes are more complex, associated with neutrophilic or lymphocytic infiltrations with/without damage to the adjacent alveolar walls. Foamy macrophage responses induced by inhaled drugs may be ascribed to either phagocytosis of poorly soluble drug particles, or to pharmacology. Both corticosteroids and β2 -agonists increase surfactant synthesis whereas muscarinic antagonists may decrease surfactant breakdown, due to inhibition of phospholipase C, both of which lead to phagocytosis of excess surfactant. Simple foamy macrophage responses are considered non-adverse, whereas ones that are more complex are designated as adverse. The development of foamy macrophage responses has led to confusion in interpretation and we hope this review helps clarify what is in fact a relatively simple, predictable, easily interpretable, commonly induced change.

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“…Surfactant lipids inhibit NF-κβ activation and increase macrophage production of the anti-inflammatory cytokine IL-10 following LPS exposure (10). In addition to AM immunoregulation by surfactant components, AMs are active in surfactant lipid catabolism (24, 25) and are indispensable for surfactant homeostasis (26, 27). Due to the prominent role of surfactant in shaping the AM immune response repertoire and the contributions of AMs to pulmonary homeostasis, it is crucial to incorporate aspects of the lung environment, such as surfactant, into experiments addressing macrophage responses to M.tb , a predominantly pulmonary pathogen.…”

Section: Introductionmentioning

confidence: 99%

CD36-Mediated Uptake of Surfactant Lipids by Human Macrophages Promotes Intracellular Growth of Mycobacterium tuberculosis

Dodd

Pyle

Glowinski

et al. 2016

The Journal of Immunology

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Mycobacterium tuberculosis (M.tb) imposes a large global health burden as the airborne agent of tuberculosis. M.tb has been flourishing in human populations for millennia and is therefore highly adapted to the lung environment. Alveolar macrophages (AMs), a major host cell niche for M.tb, not only phagocytose inhaled microbes and particulate matter but are also crucial in catabolizing lung surfactant, a lipid-protein complex that lines the alveolar spaces. Since macrophage host defense properties can be regulated by surfactant and M.tb can use host lipids as a carbon source during infection, we sought to determine the receptor(s) involved in surfactant lipid uptake by human macrophages and whether the presence of those lipids within macrophages prior to infection with M.tb enhances bacterial growth. We show that preformed scavenger receptor CD36 is redistributed to the cell membrane following exposure to surfactant lipids and surfactant protein A (SP-A). Subsequently, surfactant lipids and/or SP-A enhance CD36 transcript and protein levels. We show that CD36 participates in surfactant lipid uptake by human macrophages, as CD36 knockdown reduces uptake of dipalmitoylphosphatidylcholine (DPPC), the most prevalent surfactant lipid species. Finally, exposing human macrophages to surfactant lipids prior to infection augments M.tb growth in a CD36-dependent manner. Thus, we provide evidence that CD36 mediates surfactant lipid uptake by human macrophages and that M.tb exploits this function for growth.

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The role of alveolar macrophages in surfactant turnover

Cited by 28 publications

References 13 publications

Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution

Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution

Foamy macrophage responses in the rat lung following exposure to inhaled pharmaceuticals: a simple, pragmatic approach for inhaled drug development

CD36-Mediated Uptake of Surfactant Lipids by Human Macrophages Promotes Intracellular Growth of Mycobacterium tuberculosis

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