Hemozoin impairs cell cycle progression and promotes chemokine release in human microvascular endothelial cells

Nicoletta Basilico,Daniela Girelli,Sarah D’Alessandro,Mauro Prato,Silvia Carluccio,Donatella Taramelli,Yolanda Corbett,Serena Del Bue,Pasquale Ferrante

doi:10.1186/1475-2875-11-s1-p9

Abstract

Background Cerebral malaria (CM) is a fatal complication of P. falciparum infection caused by the cytoadherence of infected erythrocytes to brain endothelial cells followed by microcirculatory obstruction, blood-brain barrier (BBB) damage, ring hemorrhages, inflammatory response and neurological sequelae. The combination of both parasite and host factors are involved in the pathogenesis of CM. In particular, malarial pigment, hemozoin (HZ) was shown to interfere with monocytes and endothelial cell functions. Recently our group demonstrated that HZ enhanced total gelatinolytic activity in endothelial cells by inducing ex novo matrix metalloproteinases-9 (MMP9) and promoting proMMP-9 protein expression (Prato et al., 2011).

Highlights

Cerebral malaria (CM) is a fatal complication of P. falciparum infection caused by the cytoadherence of infected erythrocytes to brain endothelial cells followed by microcirculatory obstruction, blood-brain barrier (BBB) damage, ring hemorrhages, inflammatory response and neurological sequelae
Cell morphology was evaluated by optical microscopy, chemokine (CXCL-8, CCL-5) production by ELISA, proliferation/viability by MTT assay and trypan blue count, apoptosis and cell cycle by FACS analysis, using Annexin Vl Propidium Iodide (PI) and only PI, respectively
Neutrophils/monocytes recruitment is favoured resulting in the amplification of the inflammatory response

Summary

Background

Cerebral malaria (CM) is a fatal complication of P. falciparum infection caused by the cytoadherence of infected erythrocytes to brain endothelial cells followed by microcirculatory obstruction, blood-brain barrier (BBB) damage, ring hemorrhages, inflammatory response and neurological sequelae. The combination of both parasite and host factors are involved in the pathogenesis of CM. Malarial pigment, hemozoin (HZ) was shown to interfere with monocytes and endothelial cell functions. Our group demonstrated that HZ enhanced total gelatinolytic activity in endothelial cells by inducing ex novo matrix metalloproteinases-9 (MMP9) and promoting proMMP-9 protein expression (Prato et al, 2011)

Materials and methods

Conclusions

Results