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Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals

Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plas...

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Autores principales: Lautenschlager, Sueli de Oliveira Silva, Kim, Tehyung, Bidóia, Danielle Lazarim, Nakamura, Celso Vataru, Anders, Hans-Joachim, Steiger, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017347/
https://www.ncbi.nlm.nih.gov/pubmed/31905972
http://dx.doi.org/10.3390/cells9010093
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author Lautenschlager, Sueli de Oliveira Silva
Kim, Tehyung
Bidóia, Danielle Lazarim
Nakamura, Celso Vataru
Anders, Hans-Joachim
Steiger, Stefanie
author_facet Lautenschlager, Sueli de Oliveira Silva
Kim, Tehyung
Bidóia, Danielle Lazarim
Nakamura, Celso Vataru
Anders, Hans-Joachim
Steiger, Stefanie
author_sort Lautenschlager, Sueli de Oliveira Silva
collection PubMed
description Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1–1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the plasma effect. Taken together, neutrophils cleared hemozoin crystals from the extracellular space via endocytosis into phagosomes and vesicles without inducing the release of neutrophil extracellular traps. However, human plasma components such as fibrinogen limited hemozoin clearance, whereas the presence of platelets augmented this process. These factors may influence the pro-inflammatory potential of hemozoin crystals in malaria.
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spelling pubmed-70173472020-02-28 Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals Lautenschlager, Sueli de Oliveira Silva Kim, Tehyung Bidóia, Danielle Lazarim Nakamura, Celso Vataru Anders, Hans-Joachim Steiger, Stefanie Cells Article Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1–1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the plasma effect. Taken together, neutrophils cleared hemozoin crystals from the extracellular space via endocytosis into phagosomes and vesicles without inducing the release of neutrophil extracellular traps. However, human plasma components such as fibrinogen limited hemozoin clearance, whereas the presence of platelets augmented this process. These factors may influence the pro-inflammatory potential of hemozoin crystals in malaria. MDPI 2019-12-30 /pmc/articles/PMC7017347/ /pubmed/31905972 http://dx.doi.org/10.3390/cells9010093 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lautenschlager, Sueli de Oliveira Silva
Kim, Tehyung
Bidóia, Danielle Lazarim
Nakamura, Celso Vataru
Anders, Hans-Joachim
Steiger, Stefanie
Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
title Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
title_full Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
title_fullStr Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
title_full_unstemmed Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
title_short Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
title_sort plasma proteins and platelets modulate neutrophil clearance of malaria-related hemozoin crystals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017347/
https://www.ncbi.nlm.nih.gov/pubmed/31905972
http://dx.doi.org/10.3390/cells9010093
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