Medicine (RMH) - Research Publications

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Author: Boeuf, Philippe × Author: Brown, Graham × Start date: 1980 × Type: Journal Article ×

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    Soluble CD163, a Product of Monocyte/Macrophage Activation, Is Inversely Associated with Haemoglobin Levels in Placental Malaria
    Chua, CLL ; Brown, GV ; Hamilton, JA ; Molyneux, ME ; Rogerson, SJ ; Boeuf, P ; LUTY, AJF (PUBLIC LIBRARY SCIENCE, 2013-05-22)
    In Plasmodium falciparum malaria, activation of monocytes and macrophages (monocytes/macrophages) can result in the production of various inflammatory mediators that contribute to immunopathology. Soluble CD163 (sCD163) is a specific marker of monocyte/macrophage activation typically found at increased levels during various inflammatory conditions and can be associated with poor clinical outcomes. To better understand the relationships between levels of sCD163 and clinical parameters in women with placental malaria, we measured plasma sCD163 levels in maternal peripheral and placental blood compartments at delivery and determined their correlations with birth weight and maternal haemoglobin concentrations. sCD163 levels were negatively correlated with birth weight only in the placental compartment (r = -0.145, p = 0.03) and were inversely correlated with maternal haemoglobin concentrations, both in peripheral blood (r = -0.238, p = 0.0004) and in placental blood (r = -0.259, p = 0.0001). These inverse relationships suggest a potential role for monocyte/macrophage activation in the pathogenesis of malaria in pregnancy, particularly in relation to malaria-associated anaemia.
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    Plasmodium falciparum Malaria Elicits Inflammatory Responses that Dysregulate Placental Amino Acid Transport
    Boeuf, P ; Aitken, EH ; Chandrasiri, U ; Chua, CLL ; McInerney, B ; McQuade, L ; Duffy, M ; Molyneux, M ; Brown, G ; Glazier, J ; Rogerson, SJ ; Kazura, JW (PUBLIC LIBRARY SCIENCE, 2013-02)
    Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na⁺-dependent ¹⁴C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM.