Immunopathological effects of malaria pigment or hemozoin and other crystals

Our plain-English summary of Immunopathological effects of malaria pigment or hemozoin and other crystals, by A. Tyberghein, K. Deroost, E. Schwarzer, et al (BioFactors, 2014).

The study

• Authors: A. Tyberghein, K. Deroost, E. Schwarzer, P. Arese, P.E. Van den Steen
• Journal: BioFactors
• Published: 2014;40(1):59-78
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Blood-stage malaria parasites produce insoluble hemozoin (Hz) crystals that are released in the blood circulation upon schizont rupture. In general, endogenous crystal formation or inhalation of crystalline materials is often associated with pathology. As the immune system responds differently to crystalline particles than to soluble molecules, in this review, the properties, immunological recognition, and pathogenic responses of Hz are discussed, and compared with two other major pathogenic crystals, monosodium urate (MSU) and asbestos. Because of the size and shape of MSU crystals and asbestos fibers, phagolysosomal formation is inefficient and often results in leakage of lysosomal content in the cell cytoplasm and/or in the extracellular environment with subsequent cell damage and cell death. Phagolysosomal formation after Hz ingestion is normal, but Hz remains stored inside these cells for months or even longer without any detectable degradation. Nonetheless, the different types of crystals are recognized by similar immune receptors, involving Toll-like receptors, the inflammasome, antibodies, and/or complement factors, and through similar signaling cascades, they activate both proinflammatory and anti-inflammatory immune responses that contribute to inflammation-associated pathology.

© 2013 International Union of Biochemistry and Molecular Biology.

In plain English

This article was a review, not a new study. The authors compared published research on immune responses to three kinds of crystals: hemozoin, a pigment made by malaria parasites; monosodium urate (MSU) crystals, which cause gout; and inhaled asbestos fibers. The article did not say how the studies were chosen or how many were included. The review described amphibole asbestos fibers as considered more toxic than chrysotile fibers. Because amphiboles have the highest iron content, it called them the most potent producers of reactive oxygen species (chemically reactive molecules). According to the review, asbestos fibers and MSU crystals, because of their large size, damage the cell compartment that encloses swallowed material or cannot be fully swallowed ('frustrated phagocytosis'), releasing lysosomal (digestive) content into the cell's interior or outside the cell. Cells that swallow hemozoin stay alive but keep the pigment for long periods. Asbestos was described as activating an immune sensor called the NLRP3 inflammasome. The authors concluded that cell death from frustrated phagocytosis is the most significant difference between the crystals. They noted conflicting results and mechanisms that are not fully understood.

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: Review article (narrative literature review comparing three crystals); no original data on people
• Who was studied: No study population. The authors reviewed published cellular, animal and human research on hemozoin, MSU crystals and asbestos. No search method or number of studies was reported.
• Exposure: Hemozoin (malaria pigment), compared with monosodium urate crystals and asbestos fibers (chrysotile and amphibole types)
• Main results:
  • The review described asbestos and MSU crystals as causing frustrated phagocytosis. Because of their large size, these crystals damage the phagolysosome (the cell compartment that encloses swallowed material) or cannot be completely swallowed. This leads to release of lysosomal content into the cytosol or outside the cell.
  • The review stated that amphibole fibers are considered more toxic than chrysotile fibers. The reasons given were that amphiboles collect deeper in the lungs, are cleared less effectively and last longer.
  • The review stated that amphibole fibers have the highest iron content and are therefore the most potent producers of reactive oxygen species.
  • The review described asbestos and silica as activating the NLRP3 inflammasome, an immune sensor inside cells.
  • In contrast to asbestos, the review described natural hemozoin as persisting inside the cells that swallowed it for long periods of time.
• The authors' conclusion: The authors concluded that, after the crystals are swallowed by cells, the most significant difference between them is that asbestos and MSU crystals eventually cause cell death through frustrated phagocytosis.
• Limitations the authors state:
  • The authors stated that conflicting data from cell and animal malaria models leave the role of hemozoin unclear.
  • The authors stated that different hemozoin preparation and purification methods produce divergent and often conflicting results.
  • The authors stated that the exact steps by which crystals activate the NLRP3 inflammasome are not completely understood.

Topics

Medical terms in this study, explained in our Lexicon: Crystalline, Pathology, Inflammation.

Related studies

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• Malarial pigment hemozoin and the innate inflammatory response — M. Olivier, K. Van Den Ham, et al. (2014)
• Recent developments in immune activation by uric acid crystals — G. Ng, E.M. Chau, et al. (2010)

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