Circulating Red Cell–derived Microparticles in Human Malaria

Abstract

In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell-derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13-4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281-503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127-200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3-166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs.

Current Advances in Cerebral Malaria Associated Encephalopathy

“…pRBCs released 10 times more RMPs than did URBCs. Overall, the majority of RMPs were derived from URBCs (Nantakomol, Dondorp et al 2011). In vitro, RMPs production increased as the parasites matured.…”

“…Some biological molecules can trigger RMPs release. For example, hemin-mediated oxidative stress was associated with the production of RMPs (Nantakomol, Dondorp et al 2011). Hemin induced RMP formation in URBCs was inhibited by Nacetylcysteine.…”

“…Red blood cell-derived microparticles (RMPs) were increased in patients with P. falciparum, P. vivax, and P. malariae compared with healthy controls (Nantakomol, Dondorp et al 2011). RMPs were highest in severe falciparum malaria patients.…”

Phospholipases during membrane dynamics in malaria parasites

“…Both uRBCs and iRBCs release microvesicles into the host serum, which are suggested to arise by blebbing from lipid rafts (Mantel et al, 2013;Nantakomol et al, 2011; reviewed in Mantel and Marti, 2014). These structures are likely involved in mediating cell-cell communication between parasites and in the induction of gametocyte formation (Mantel et al, 2013;Nantakomol et al, 2011;Regev-Rudzki et al, 2013).…”

“…These structures are likely involved in mediating cell-cell communication between parasites and in the induction of gametocyte formation (Mantel et al, 2013;Nantakomol et al, 2011;Regev-Rudzki et al, 2013). Isolated microvesicles exhibited enriched PS and PI levels compared to the RBCM (Gulati et al, 2015).…”