Bee venom phospholipase A(2) induces stage-specific growth arrest of the intraerythrocytic Plasmodium falciparum via modifications of human serum components

Secreted phospholipases A(2) (sPLA(2)s) from snake and insect venoms and fr om mammalian pancreas are structurally related enzymes that have been assoc iated with several toxic, pathological, or physiological processes. We addr essed the issue of whether toxic sPLA(2)s might exert specific effects on t he Plasmodium falciparum intraerythrocytic development. We showed that both toxic and non-toxic sPLA(2)s are lethal to P. falciparum grown in vitro, w ith large discrepancies between respective IC50 values; IC50 values from to xic PLA(2)s ranged from 1.1 to 200 pM, and IC50 values from non-toxic PLA(2 )s ranged from 0.14 to 1 muM. Analysis of the molecular mechanisms responsi ble for cytotoxicity of bee venom PLA(2) (toxic) and hog pancreas PLA, (non -toxic) demonstrated that, in both cases, enzymatic hydrolysis of serum pho spholipids present in the culture medium was responsible for parasite growt h arrest. However, bee PLA(2)-lipolyzed serum induced stage-specific inhibi tion of P. falciparum development, whereas hog PLA(2)-lipolyzed serum kille d parasites at either stage. Sensitivity to bee PLA(2)-treated serum appear ed restricted to the 19-26-h period of the 48 h parasite cycle. Analysis of the respective role of the different lipoprotein classes as substrates of bee PLA(2) showed that enzyme treatment of high density lipoproteins, low d ensity lipoproteins, and very low density lipoproteins/chylomicrons fractio ns induces cytotoxicity of either fraction. In conclusion, our results demo nstrate that toxic and non-toxic PLA(2)s 1) are cytotoxic to P. falciparum via hydrolysis of lipoprotein phospholipids and 2) display different killin g processes presumably involving lipoprotein by-products recognizing differ ent targets on the infected red blood cell.