Phagocytosis of the malarial pigment, hemozoin, impairs expression of major histocompatibility complex class II antigen, CD54, and CD11c in human monocytes.
In Plasmodium falciparum malaria, large proportions of resident macrophages and circulating monocytes and leukocytes contain massive amounts of the malarial pigment, hemozoin. Previous studies have shown that important functions (e.g., the generation of the oxidative burst, the ability to repeat phagocytosis, and protein kinase C activity) were severely impaired in hemozoin-loaded monocytes. Expression of membrane antigens directly involved in the immune response and in the phagocytic process, and/or under protein kinase C control, in hemozoin-loaded human monocytes was studied. Expression of major histocompatibility complex (MHC) class II after gamma interferon stimulation was blocked in hemozoin-loaded monocytes at the protein expression and gene transcription levels but was preserved in control monocytes loaded with opsonized latex beads or anti-D(Rho)-immunoglobulin G (IgG)-opsonized human erythrocytes. Expression of CD54 (intracellular adhesion molecule 1) and CD11c (p150,95 integrin) was also decreased in hemozoin-loaded monocytes. Expression of MHC class I, CD16 (low-affinity Fc receptor for aggregated IgG), CD32 (low-affinity Fc receptor for aggregated IgG), CD64 (high-affinity receptor for IgG), CD11b (receptor for complement component iC3b [CR3]), CD35 (receptor for complement components C3b and C4b [CR1]), and CD36 (non-class-A scavenger receptor) was not specifically affected by hemozoin loading. These results suggest that hemozoin loading may contribute to the impairment of the immune response and the derangement of antigen presentation reported in previous studies of P. falciparum malaria.
Schwarzer
E
E
Department of Genetics, Biology and Biochemistry, University of Turin Medical School, Italy.
Alessio
M
M
Ulliers
D
D
Arese
P
P
D000328:Adult; D005260:Female; D006420:Hemeproteins / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000032:analysis*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D010860:Pigments, Biological / Q000502:physiology*
D006420:Hemeproteins; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2; D010860:Pigments, Biological; D018799:Intercellular Adhesion Molecule-1; C020753:hemozoin; D007371:Interferon-gamma