Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice

Nagre, Nagaraja N.; Cong, Xiaofei; Pearson, Andrew C.; Zhao, Xiaoli

doi:10.3791/59088

Cited by 17 publications

(14 citation statements)

References 18 publications

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“…2021 ). This is due to the site of deposition and limited clearance mechanisms, which in the case of alveoli entails engulfment by macrophages only, with a clearance process of insoluble particles occurring over months to years ( Hinds 1999 ; Nagre et al. 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Insoluble particles <10 lm, which can reach and deposit in large numbers in the alveolar region, may cause inflammation and systemic changes even if the material they are composed of is not potentially toxic (Garcés et al 2021). This is due to the site of deposition and limited clearance mechanisms, which in the case of alveoli entails engulfment by macrophages only, with a clearance process of insoluble particles occurring over months to years (Hinds 1999;Nagre et al 2019). Plastic particles may serve as carriers of mixtures of chemicals ad-and absorbed on them.…”

Section: Toxicologymentioning

confidence: 99%

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A Children’s Health Perspective on Nano- and Microplastics

Sripada

Wierzbicka

Abass

et al. 2022

Environ Health Perspect

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Background: Pregnancy, infancy, and childhood are sensitive windows for environmental exposures. Yet the health effects of exposure to nano- and microplastics (NMPs) remain largely uninvestigated or unknown. Although plastic chemicals are a well-established research topic, the impacts of plastic particles are unexplored, especially with regard to early life exposures. Objectives: This commentary aims to summarize the knowns and unknowns around child- and pregnancy-relevant exposures to NMPs via inhalation, placental transfer, ingestion and breastmilk, and dermal absorption. Methods: A comprehensive literature search to map the state of the science on NMPs found 37 primary research articles on the health relevance of NMPs during early life and revealed major knowledge gaps in the field. We discuss opportunities and challenges for quantifying child-specific exposures (e.g., NMPs in breastmilk or infant formula) and health effects, in light of global inequalities in baby bottle use, consumption of packaged foods, air pollution, hazardous plastic disposal, and regulatory safeguards. We also summarize research needs for linking child health and NMP exposures and address the unknowns in the context of public health action. Discussion: Few studies have addressed child-specific sources of exposure, and exposure estimates currently rely on generic assumptions rather than empirical measurements. Furthermore, toxicological research on NMPs has not specifically focused on child health, yet children’s immature defense mechanisms make them particularly vulnerable. Apart from few studies investigating the placental transfer of NMPs, the physicochemical properties (e.g., polymer, size, shape, charge) driving the absorption, biodistribution, and elimination in early life have yet to be benchmarked. Accordingly, the evidence base regarding the potential health impacts of NMPs in early life remains sparse. Based on the evidence to date, we provide recommendations to fill research gaps, stimulate policymakers and industry to address the safety of NMPs, and point to opportunities for families to reduce early life exposures to plastic. https://doi.org/10.1289/EHP9086

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Section: Discussionmentioning

confidence: 99%

Section: Toxicologymentioning

confidence: 99%

A Children’s Health Perspective on Nano- and Microplastics

Sripada

Wierzbicka

Abass

et al. 2022

Environ Health Perspect

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“…The tissue-resident alveolar macrophages (AMs) are unique because they directly communicate with the environment and defend the lungs against broad-spectrum and antibiotic-resistant species of Gram-negative bacteria, including Pseudomonas aeruginosa ( PA , hence forth) ( Restrepo et al, 1999 ; Moraes et al, 2008 ; Nagre et al, 2019 ). PA , being an extracellular pathogen, prefers to associate with the surface of the host cell membrane ( Lillehoj et al, 2001 ; Siryaporn et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Protease-activated receptor 2 promotes clearance of Pseudomonas aeruginosa infection by inducing cAMP-Rac1 signaling in alveolar macrophages

Rayees

Joshi²,

Joshi³

et al. 2022

Front. Pharmacol.

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Efficient phagocytosis of pathogens by the innate immune system during infectious injury is vital for restoring tissue integrity. Impaired phagocytosis, such as in the case of infection with Pseudomonas aeruginosa, a broad-spectrum antibiotic-resistant Gram-negative bacterium, can lead to a life threatening lung disorder, acute lung injury (ALI). Evidence indicates that loss of protease-activated receptor 2 (PAR2) impaired Pseudomonas aeruginosa clearance leading to non-resolvable ALI, but the mechanism remains unclear. Here, we focused on the alveolar macrophages (AMs), the predominant population of lung-resident macrophages involved in sensing bacteria, to understand their role in PAR2-mediated phagocytosis of Pseudomonas aeruginosa. We found that upon binding Pseudomonas aeruginosa, PAR2-expressing but not PAR2-null AMs had increased cAMP levels, which activated Rac1 through protein kinase A. Activated Rac1 increased actin-rich protrusions to augment the phagocytosis of Pseudomonas aeruginosa. Administration of liposomes containing constitutively active Rac1 into PAR2-null mice lungs rescued phagocytosis and enhanced the survival of PAR2-null mice from pneumonia. These studies showed that PAR2 drives the cAMP-Rac1 signaling cascade that activates Pseudomonas aeruginosa phagocytosis in AMs, thereby preventing death from bacterial pneumonia.

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“…The defining feature of AM is their ability to phagocytize substances in the air spaces ( 40 ), so we examined whether these different AM subsets differed at ingesting pneumococcus in experienced lungs. Mismatched serotypes precluded opsonophagocytosis driven by antibodies against capsular polysaccharides.…”

Section: Resultsmentioning

confidence: 99%