PHAGOCYTOSIS OF THE MALARIAL PIGMENT, HEMOZOIN, IMPAIRS EXPRESSION OFMAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN, CD54, AND CD11C INHUMAN MONOCYTES

In Plasmodium falciparum malaria, large proportions of resident macrop hages and circulating monocytes and leukocytes contain massive amounts of the malarial pigment, hemozoin. Previous studies have shown that i mportant functions (e.g., the generation of the oxidative burst, the a bility to repeat phagocytosis, and protein kinase C activity) were sev erely impaired in hemozoin-loaded monocytes. Expression of membrane an tigens directly involved in the immune response and in the phagocytic process, and/or under protein kinase C control, in hemozoin-loaded hum an monocytes was studied. Expression of major histocompatibility compl ex (MHC) class II after gamma interferon stimulation was blocked in he mozoin-loaded monocytes at the protein expression and gene transcripti on levels but was preserved in control monocytes loaded with opsonized latex beads or anti-D(Rh-o)-immunoglobulin G(IgG)-opsonized human ery throcytes. Expression of CD54 (intracellular adhesion molecule 1) and CD11c (p150,95 integrin) was also decreased in hemozoin-loaded monocyt es. Expression of MHC class I, CD16 (low-affinity Fc receptor for aggr egated IgG), CD32 (low-affinity Fc receptor for aggregated IgG), CD64 (high-affinity receptor for IgG), CD11b (receptor for complement compo nent iC3b [CR3]), CD35 (receptor for complement components C3b and C4b [CR1]), and CD36 (non-class-A scavenger receptor) was not specificall y affected by hemozoin loading. These results suggest that hemozoin lo ading may contribute to the impairment of the immune response and the derangement of antigen presentation reported in previous studies of P. falciparum malaria.