Table 1 Phenotype of endothelial cells after co-culture with infected red blood cells in vitro

Porcine brain capillary endothelial cells (PBCEC)

P. falciparum

- ICAM-1, E-selectin expression;

- increased ICAM-1 and E-selectin

[99]

- TEER;

- decreased BBB function;

- tight junction expression

- tight junction disruption

Human umbilical vascular endothelial cells (HUVEC) co-cultured with iRBC-fed peripheral blood mononuclear cells

P. falciparum from patients with uncomplicated malaria, severe malaria, or CM

mRNA expression of:

- increased adhesion molecule mRNA (not CM-specific);

[100]

- adhesion molecules (ICAM-1, VCAM-1, E-selectin);

- reduced tight junction mRNA (CM-specific)

- tight junctions (occludin, vinculin, ZO-1)

TNF-α- or LT-α-activated human brain endothelial cell line (HBEC-5i) (with/without platelet co-culture)

P. falciparum

- permeability to 70-kDa dextran;

- increased BBB permeability;

[101]

- TEER;

- decreased BBB function;

- endothelial microparticle release;

- increased microparticle release;

- endothelial apoptosis

- increased endothelial apoptosis (all effects potentiated by platelets)

Human brain microvascular endothelial cells (HBMEC); HUVEC

P. falciparum

- ICAM-1 expression

increased ICAM-1 expression in HBMEC but not in HUVEC

[93]

HBMEC

P. falciparum

- electrical cell substrate sensing;

- reduced BBB function;

[102]

- TEER

- increased BBB permeability

Human dermal microvascular endothelial cells (HDMEC); human lung microvascular endothelial cells (HLMEC) (with parasite sonicates or iRBCs)

P. falciparum

- immunofluorescence staining of ZO-1, claudin-5, VE-cadherin;

- loss in total protein content of claudin-5;

[103]

- observation of inter-endothelial gaps in monolayers;

- redistribution of ZO-1 from cytoskeleton to membrane and cytosolic/nuclear fractions;

- evaluation of pro-inflammatory response, direct cellular cytotoxicity or cell death.

- minimal inflammation and death (all effects only with sonicates)

HBMEC

P. falciparum

- expression of transcriptome (including ICAM-1 and pro-inflammatory molecules)

- increased expression of ICAM-1 and pro-inflammatory molecules

[104]

HBEC-5i; immortalized human cerebral microvascular cell line hCMEC/D3

P. falciparum

- immunofluorescent microscopy to evaluate malaria antigen presentation by endothelial cells;

- malaria antigen presentation by endothelial cells;

[56]

- tight junction opening;

- TEER

- increased BBB permeability

hCMEC/D3

P. falciparum

- fluorescent permeability assay;

- increased BBB permeability;

[105]

- expression of cell adhesion molecules and tight junctions

- increased ICAM-1 expression;

- cytoadherence;

- altered ZO-1 distribution

TNF-α-activated subcutaneous fat tissue-derived EC from patients with uncomplicated malaria or CM

P. falciparum

- adhesion molecule expression (ICAM-1, VCAM-1, CD61, CD62-E)

- higher ICAM-1, VCAM-1, CD61;

[106]

- enhanced microparticle release;

- microparticle production;

- induced MCP-1 and IL-6 release;

- MCP-1, RANTES, IL-6 release ;

- higher caspase-3 activation (all effects CM-specific)

- caspase-3 activation

HBEC-5i

P. falciparum (various strains)

parasite strain selection assay based on cytoadherence

CM-associated cytoadherence

[107]

Murine brain vascular endothelial cells (MBVEC) murine lung vascular endothelial cells (MLVEC)

P. berghei ANKA (CM model); P. berghei K173 (non-CM model)

- study of cytoadherence mechanisms;

higher VCAM-1-mediated cytoadherence in CM model compared to non-CM model

[108]