<it>Plasmodium vivax</it>: paroxysm-associated lipids mediate leukocyte aggregation

• Main Authors: Mendis Kamini, Chandrasekharan Vishvanath, Wanasekara Deepani, Karunaweera Nadira, Carter Richard
• Format: Article
• Language: English
• Published: BMC 2007-05-01
• Series: Malaria Journal
• Online Access: http://www.malariajournal.com/content/6/1/62

<p>Abstract</p> <p>Background</p> <p>Paroxysms are recurrent febrile episodes, characteristic of <it>Plasmodium vivax </it>infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes <it>in vitro </it>in the presence of parasite and host factors released during paroxysms.</p> <p>Methods</p> <p>Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms.</p> <p>Results</p> <p>Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute <it>P. vivax </it>infections was neutralized by immune sera raised against schizont extracts of either <it>P. vivax </it>or <it>Plasmodium falciparum</it>. However, immune sera against <it>P. vivax </it>were more effective than that against <it>P. falciparum </it>indicating that the parasite activity involved may be antigenically at least partially parasite species-specific.</p> <p>Conclusion</p> <p>Leukocyte aggregation was identified as associated with paroxysms in <it>P. vivax </it>infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of <it>P. vivax </it>malaria.</p>