Polymorphonuclear leucocytes defective in oxidative metabolism inhibit in vitro growth of Plasmodium falciparum. Evidence against an oxygen-dependent mechanism.

Abstract

This report presents evidence that polymorphonuclear leucocytes (PMN) from chronic granulomatous disease (CGD) patients, who are defective in oxidative metabolism, are capable of inhibiting in vitro multiplication of Plasmodium falciparum. Using a microtitre in vitro inhibition assay, we incubated various numbers of peripheral blood neutrophils from CGD patients and from normal individuals with P. falciparum isolate F32 in the in vitro culture system. Inhibition of parasite growth by neutrophils was determined after 48 h of culture. At PMN to erythrocyte ratio of 1:50 there was an inhibition of parasite growth of 57% by normal neutrophils and 39% to 68% by CGD cells. When the neutrophils were stimulated by phorbol myristate acetate, both cell types enhanced inhibition of parasite growth. These findings indicate that the oxygen-independent systems of human neutrophils are involved in parasite destruction. Constituents of neutrophil granules such as acid hydrolases, lactoferrin, and cationic proteins could be regarded as potential mediators of parasite destruction.