In vivo acquisition of hemozoin by placental blood mononuclear cells suppresses PGE2, TNF-alpha, and IL-10.
In areas of high malaria endemicity, women have increased susceptibility to malaria during pregnancy characterized by placental parasitemia. Our previous studies in children with malaria demonstrate that suppression of leukocyte-derived prostaglandin-E(2) (PGE(2)) is associated with enhanced pathogenesis. To examine the role of PGE(2) as an immunoregulatory molecule in placental malaria, PGE(2) was determined in cultured intervillous blood mononuclear cells (IVBMCs) from aparasitemic and parasitemic women. PGE(2) was significantly lower in parasitemic women at all gravidities. Women with a positive antenatal peripheral parasitemia who were negative for placental malaria (PM) at term produced the highest PGE(2) levels. Suppression of PGE(2) was associated with increasing amounts of hemozoin (malarial pigment) acquired during the natural infection. PGE(2) regulatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, were non-significantly increased in IVBMC containing an intermediate amount of hemozoin and significantly suppressed in IVBMC with high levels of hemozoin. Results presented here show that in vivo acquisition of high levels of hemozoin by IVBMC leads to decreased synthesis of PGE(2), IL-10, and TNF-alpha.
Perkins
Douglas J
DJ
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Moore
Julie M
JM
Otieno
Juliana
J
Shi
Ya Ping
YP
Nahlen
Bernard L
BL
Udhayakumar
Venkatachalam
V
Lal
Altaf A
AA
D002478:Cells, Cultured; D002824:Chorionic Villi / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006420:Hemeproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008288:Malaria / Q000097:blood / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010922:Placenta Diseases / Q000097:blood / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D010940:Plant Proteins; D011247:Pregnancy; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D006420:Hemeproteins; D010835:Phytohemagglutinins; D010940:Plant Proteins; D014409:Tumor Necrosis Factor-alpha; C101135:phytohemagglutinin L protein, Phaseolus vulgaris; D016753:Interleukin-10; C020753:hemozoin; D015232:Dinoprostone