Macrophage Recognition of Crystals and Nanoparticles

Our plain-English summary of Macrophage Recognition of Crystals and Nanoparticles, by M. Nakayama (Frontiers in Immunology, 2018).

The study

• Author: M. Nakayama
• Journal: Frontiers in Immunology
• Published: 2018;9:103
• Type of article: Review
• Cited by: 118 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles. Several recent studies have reported that some crystal particles are negatively charged and are recognized by scavenger receptor family members in a charge-dependent manner. Alternatively, a model for receptor-independent phagocytosis of crystals has also been proposed. This review focuses on the mechanisms by which macrophages recognize crystals and nanoparticles.

In plain English

This article was a review by a single author, not a new study. It summarized published laboratory and animal research on how macrophages, immune cells that engulf foreign particles, recognize crystals and nanoparticles. These included silica, asbestos, carbon nanotubes, titanium particles and alum, and crystals formed in the body: monosodium urate, cholesterol and hydroxyapatite. The review stated that macrophages take up asbestos, leading to activation of an inflammatory protein complex called the NLRP3 inflammasome and to cell death. It described a study by Murthy and colleagues in which mice lacking a receptor called MARCO showed less fibrosis after chrysotile asbestos exposure, although that study did not show MARCO binding asbestos directly. It also described a study in which multi-walled carbon nanotubes injected into the abdominal cavity caused mesothelioma in genetically modified p53+/– mice. The author proposed that a chain of cell death may matter more than NLRP3 activation in chronic fibrosis. The author concluded that the known recognition pathways explain only a fraction of crystal uptake and that many others remain to be identified.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies; no new data
• Who was studied: Published cell, laboratory and animal studies on how macrophages recognize crystals and nanoparticles; the author studied no human or animal population for this article
• Exposure: Exogenous particles (silica, asbestos including chrysotile, carbon nanotubes, titanium nanoparticles, alum) and endogenous crystals (monosodium urate, cholesterol, hydroxyapatite)
• Main results:
  • The review stated, citing earlier work, that macrophages take up asbestos, leading to NLRP3 inflammasome activation and cell death
  • The review described a study by Murthy et al. in which MARCO-deficient mice showed less fibrosis after chrysotile asbestos exposure. That study did not show direct binding of MARCO to asbestos
  • The review described a study by Takagi et al. in which multi-walled carbon nanotubes injected into the abdominal cavity caused mesothelioma in p53+/– mice
  • The review reported that the author's laboratory had earlier identified SR-B1 as a receptor for silica. This was a prior study, not new data in this article
  • The author proposed that sequential macrophage cell death may be more crucial than NLRP3 activation in crystal-induced chronic inflammation and fibrosis, because diseases including asbestosis develop in NLRP3-deficient mice
• The authors' conclusion: The author concluded that the known recognition pathways (cell-surface receptors and membrane cholesterol) account for only a fraction of crystal uptake by macrophages, and that many unknown pathways remain to be identified
• Limitations the authors state:
  • The author noted that it remains unknown how macrophages recognize carbon nanotubes on their surface
  • The author noted that it remains unknown how particle properties such as element and size affect lysosomal damage

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Fibrosis, Phagocytosis.

Related studies

• The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine — L. Baron, A. Gombault, et al. (2015)
• An in vitro testing strategy towards mimicking the inhalation of high aspect ratio nanoparticles — C. Endes, O. Schmid, et al. (2014)
• Cytotoxic effects of some mineral dusts on Syrian hamster peritoneal macrophages — E. Bey, J.S. Harington (1971)
• Interleukin 1 production and accessory cell function of rat alveolar macrophages exposed to mineral dust particles — Y. Oghiso, Y. Kubota (1987)
• Macrophage functions after exposure to mineral fibers — F. Tilkes, E.G. Beck (1983)
• Secretion of fibronectin by mineral dust-derived alveolar macrophages and activated peritoneal macrophages — R. Davies, G. Erdogdu (1989)

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