Antimalarial activity of human group IIA secreted phospholipase A2 in relation with enzymatic hydrolysis of oxidized lipoproteins

The human group IIA secreted phospholipase A2 (hGIIA sPLA2) is increased in the plasma of malaria patients but its role is unknown. In parasite culture with normal plasma, hGIIA is inactive against Plasmodium falciparum, contrasting with hGIIF, hGV and hGX sPLA2s that readily hydrolyze plasma lipoproteins, release non-esterified fatty acids (NEFAs) and inhibit parasite growth. Here, we revisited the anti-Plasmodium activity of hGIIA in conditions closer to malaria physiopathology where lipoproteins are oxidized. In parasite culture containing oxidized lipoproteins, hGIIA sPLA2 was inhibitory with an IC50 value of 150.0 ± 40.8 nM, in accordance with its capacity to release NEFAs from oxidized particles. With oxidized lipoproteins, hGIIF, hGV and hGX sPLA2s were also more potent, by 4.6-, 2.1- and 1.9-fold, respectively. Using specific immunoassays, we found that hGIIA sPLA2 is increased in plasma from 41 patients with malaria over healthy donors (median (IQR): 1.6 (0.7-3.4) nM, versus 0.0 (0.0-0.1) nM, respectively; P In conclusion, we propose that malaria-induced oxidation of lipoproteins converts these latters into a preferential substrate for hGIIA sPLA2, promoting its parasite killing effect. This mechanism may contribute to host defense against P. falciparum in malaria where high levels of hGIIA are observed.