Alveolar macrophage development in mice requires L-plastin for cellular localization in alveoli

Todd, Elizabeth M.; Zhou, Julie Y.; Szasz, Taylor P.; Deady, Lauren E.; D’Angelo, June A.; Cheung, Matthew D.; Kim, Alfred H.J.; Morley, Sharon Celeste

doi:10.1182/blood-2016-03-705962

Cited by 49 publications

(61 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…N.S., no significant difference. contribution of the CCL2-CCR2 axis to blood monocyte migration into the lung and subsequent differentiation into AMs (8,54). In this lung metastasis model, CCL2 was produced by IMs, and AMs expressed CCR2.…”

Section: Discussionmentioning

confidence: 90%

Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating Leukotriene B4

Nosaka

Baba

Tanabe

et al. 2018

The Journal of Immunology

View full text Add to dashboard Cite

Macrophages in lungs can be classified into two subpopulations, alveolar macrophages (AMs) and interstitial macrophages (IMs), which reside in the alveolar and interstitial spaces, respectively. Accumulating evidence indicates the involvement of IMs in lung metastasis, but the roles of AMs in lung metastasis still remain elusive. An i.v. injection of a mouse hepatocellular carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of AMs and IMs. Comprehensive determination of arachidonic acid metabolite levels revealed increases in leukotrienes and PGs in lungs in this metastasis model. A 5-lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the numbers of metastatic foci, particularly those of a larger size. A major 5-LOX metabolite, LTB, augmented in vitro cell proliferation of human HCC cell lines as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited higher expression levels of the 5-LOX and LTB than IMs. Consistently, 5-LOX-expressing AMs increased in the lungs of human HCC patients with lung metastasis, compared with those without lung metastasis. Furthermore, intratracheal clodronate liposome injection selectively depleted AMs but not IMs, together with reduced LTB content and metastatic foci numbers in this lung metastasis process. Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood-borne, CCR2-expressing AMs into lungs. Thus, AMs can be recruited under the guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute to the progression of lung metastasis by providing a potent arachidonic acid-derived tumor growth promoting mediator, LTB.

show abstract

Section: Discussionmentioning

confidence: 90%

Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating Leukotriene B4

Nosaka

Baba

Tanabe

et al. 2018

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Unlike other macrophage subsets that populate organs prenatally, AM arise from embryonic precursors that occupy the luminal niche after the first breath . The transepithelial migration and engraftment of embryonic precursors into the airway space are dependent on l ‐plastin expression, and their differentiation into AM is critically regulated by granulocyte macrophage‐colony stimulating factor (GM‐CSF) . Patients carrying mutations in the GM‐CSF receptor (GM‐CSFR) spontaneously develop autoantibodies against GM‐CSF or its receptor, display loss of mature AM and show greater susceptibility to respiratory infections, along with increased accumulation of surfactant in the airways, leading to pulmonary alveolarproteinosis .…”

Section: Origin and Maintenance Of Airway Macrophages Function In Lunmentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

View full text Add to dashboard Cite

The lungs present a challenging immunological dilemma for the host. Anatomically positioned at the environmental interface, they are constantly exposed to antigens, pollutants and microbes, while simultaneously facilitating vital gas exchange. Remarkably, the lungs maintain a functionally healthy state, ignoring harmless inhaled proteins, adapting to toxic environmental insults and limiting immune responses to allergens and pathogenic microbes. This functional strategy of environmental adaptation maintains immune defense, reduces tissue damage, and promotes and sustains lung immune tolerance. At steady state, airway macrophages produce low levels of cytokines, and suppress the induction of innate and adaptive immunity. These cells are primary initiators of lung innate immunity and possess high phagocytic activity to clear particulate antigens and apoptotic cell debris from the airways to regulate the response to infection and inflammation. In response to epithelial injury, resident and recruited macrophages drive tissue repair. In this review, we will focus on the functional importance of macrophages in tissue homeostasis and inflammation in the lung and highlight how environmental cues alter the plasticity and function of lung airway macrophages. We will also discuss mechanisms employed by pulmonary macrophages to promote resolution of tissue inflammation, and how and when this balance is perturbed, they contribute to pathological remodeling in acute and chronic infections and diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

show abstract

“…AM precursors develop mainly from fetal monocytes, which seed the lung prior to birth and massively expand and develop into mature macrophages in response to granulocytemacrophage colony-stimulating factor (GM-CSF) and transforming growth factor ␤ (TGF-␤) after birth (18)(19)(20). A number of factors, including PPAR-␥, mTORC1, the phosphoinositide kinase PIKfyve, and L-plastin, were also recently shown to be important in AM development and function (19,(21)(22)(23)(24). Interestingly, AM appear to be essential for protection against IAV and other respiratory viral infections (25)(26)(27)(28)(29)(30)(31).…”

mentioning

confidence: 99%

PPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery following Respiratory Viral Infection

Huang

Zhu

Cheon

et al. 2019

J Virol

View full text Add to dashboard Cite

Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-␥ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-␥ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-␥ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-␥ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-␥ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-␥ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-␥ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-␥ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections.IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-␥ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-␥ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.A cute respiratory viral infections, such as influenza A virus (IAV) and respiratory syncytial virus (RSV) infections, cause severe morbidity and mortality and are among leading causes of death in children and the elderly (1, 2). Particularly, IAV

show abstract

Alveolar macrophage development in mice requires L-plastin for cellular localization in alveoli

Cited by 49 publications

References 53 publications

Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating Leukotriene B4

Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating Leukotriene B4

Airway macrophages as the guardians of tissue repair in the lung

PPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery following Respiratory Viral Infection

Contact Info

Product

Resources

About