Malaria pigment stimulates chemokine production by human microvascular endothelium

•The ability of haemozoin to induce the production of chemokines by microvascular endothelial cells was investigated.•Hemozoin, 15-HETE, fibrinogen but not the ferriprotoporphyrin IX backbone of haemozoin, induced chemokines production.•NF-κb inhibitors reduced and IL-1 enhanced chemokines production induced by haemozoin.

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.

Graphical abstractHemozoin or its derivatives/components induce chemokine production by endothelial cells. The effect was partially inhibited by NF-κb inhibitors and enhanced by inflammatory cytokines.Download high-res image (158KB)Download full-size image