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Biobased, Biodegradable but not bio-neutral: about the effects of polylactic acid nanoparticles on macrophages.

ABSTRACT: Plastics are one of the most preoccupying emerging pollutants. Macroplastics released in the environment degrade into microplastics and nanoplastics. Because of their small size, these micro and nano plastic particles can enter the food chain and, in addition to their ecotoxicological effects, contaminate humans with still poorly known biological effects. Plastics being particulate pollutants, they are handled in the human body by scavenger cells such as macrophages, which are important players in the immune system. Because of all the potential problems, it is advocated to replace fossil fuel-based plastics by bio-based and bio-degradable plastics, among which poly-hydroxyalkanoates are the most promising. However, the effects of these on mammalian cells are even less known than those of fossil fuel-based plastics. We therefore designed a study aiming at investigating the effects of polylactic acid (PLA) nanoparticles on macrophages. Indeed, being a plastic, PLA is known to fragment and liberate micro and nanoparticles, exactly as conventional plastics. These particles will be internalized by macrophages and may induce functional consequences on these cells. Proteomics showed important adaptive changes of the proteome in response to exposure to PLA, and several important pathways such as mitochondrion, lysosomes or endoplasmic reticulum were highlighted by the proteomic analysis. However, validation experiments showed that most of these changes were homeostatic and allowed the cells to keep these functions unaltered. When the inflammatory response was examined, no major increase in the secretion of tumor necrosis factor or interleukin 6 was observed. However, the secretion of these cytokines in response to lipopolysaccharide was altered after exposure to PLA. The production of interleukin 6 was decreased, while the production of tumor necrosis factor, showing a complex alteration of cellular responses after exposure to PLA nanoparticles. In conclusion, these results provide a better understanding of the responses of macrophages to exposure to the biodegradable PLA nanoparticles.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Hélène Diemer

LAB HEAD: Dr Sarah Cianferani

PROVIDER: PXD048664 | Pride | 2024-12-09

REPOSITORIES: pride

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Project description:Sulfur mustard (SM) is a potent alkylating agent. We are developing medical countermeasures to reduce the injury caused by SM exposure. Screening in the mouse ear vesicant model has identified three effective compounds: dimercaprol (British anti-lewisite), indomethacin, and octyl homovanillamide (OHV). To identify gene expression changes that correlate with compound efficacy we used oligonucleotide microarrays to compare gene expression profiles in vehicle-exposed skin, SM-exposed skin, and skin pretreated with each compound before SM exposure. Mice were topically exposed on the inner surface of the right ear to SM alone or pretreated for 15 min with one of the compounds and then exposed to SM. Left ears were vehicle-exposed. Ear tissue was harvested 24 hr later for ear weight determination (an endpoint indicating compound efficacy). The exposure groups were: methylene chloride (sulfur mustard vehicle); ethanol (drug vehicle); 0.08 mg sulfur mustard; 6.25 mg dimercaprol 15 min before 0.08 mg sulfur mustard; 1.34 mg indomethacin 15 min before 0.08 mg sulfur mustard; 0.6 mg octylhomovanillamide 15 min before 0.08 mg sulfur mustard; 6.25 mg dimercaprol alone; 1.34 mg indomethacin alone; 0.6 mg octylhomovanillamide alone. RNA was extracted from the tissues and used to generate oligonucleotide microarray probes. Principal component analysis of the gene expression data revealed partitioning of the samples based on drug treatment and SM exposure. Vehicle-exposed mouse ears clustered away from the other treatment groups. SM-exposed mouse ears pretreated with dimercaprol or OHV clustered more closely with vehicle-exposed ears, while SM-exposed mouse ears pretreated with indomethacin clustered more closely with SM-exposed ears. This clustering of the samples is supported by the ear weight data, in which the indomethacin group has ear weights closer to the SM-exposed group, whereas the dimercaprol and OHV groups have ear weights closer to the vehicle-exposed group. Correlation coefficients were calculated for each gene based on the correlation between gene expression level and ear weight. These data provide the basis for understanding what gene expression changes are important in the development of effective SM medical countermeasures. Experiment Overall Design: Exposure of mouse ears to sulfur mustard alone, sulfur mustard preceded by drug treatment, or vehicle compounds. Naive controls were also included. Biological replicates of at least n=3 were examined for each exposure condition.

			Action	DRS
	AB.mzid.gz	Mzid
	CTL.mzid.gz	Mzid
	PET.mzid.gz	Mzid
	QE44317HD.mgf	Mgf
	QE44317HD.raw	Raw

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Biobased, Biodegradable but not bio-neutral: about the effects of polylactic acid nanoparticles on macrophages.

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