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Severe falciparum malaria is characterized by the sequestration of infected erythrocytes and leukocyte recruitment in the microvasculature, resulting in impaired blood flow and metabolic disturbances. Which parasite products cause chemokine production, thus contributing to the strong host inflammatory response and cellular recruitment are not well characterized. Here, we studied haemozoin (Hz), the end-product of haem, a ferriprotoporphyrin-IX crystal bound to host and parasite lipids, DNA, and proteins. We found that natural Hz isolated from Plasmodium falciparum cultures induces CXCL8 and CCL5 production in human dermal microvascular endothelial cells (HMEC-1) in a time-dependent manner. This up-regulation is not caused by haem but rather by Hz-generated lipoperoxidation products (15-HETE) and fibrinogen associated to Hz, and is, at least in part, triggered by the activation of NF-κB, as it was significantly inhibited by artemisinin and other NF-κB pathway inhibitors.

Original publication

DOI

10.1016/j.actatropica.2017.05.002

Type

Journal

Acta tropica

Publication Date

08/2017

Volume

172

Pages

125 - 131

Addresses

Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, via Pascal 36-20133, Milano, Italy. Electronic address: nicoletta.basilico@unimi.it.

Keywords

Endothelium, Erythrocytes, Cell Line, Endothelial Cells, Animals, Humans, Plasmodium falciparum, Artemisinins, Hydroxyeicosatetraenoic Acids, Fibrinogen, Hemeproteins, Chemokines, Antimalarials, Gene Expression Regulation, Up-Regulation, Lipid Peroxidation