Lipopolysaccharide preconditioning augments phagocytosis of malaria-parasitized red blood cells by bone marrow-derived macrophages in the liver, thereby increasing the murine survival after Plasmodium yoelii infection

2021 ◽  
Author(s):  
Takeshi Ono ◽  
Yoko Yamaguchi ◽  
Hiroyuki Nakashima ◽  
Masahiro Nakashima ◽  
Takuya Ishikiriyama ◽  
...  

Malaria remains a grave concern for humans, as effective medical countermeasures for Plasmodium infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against Plasmodium infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, if LPS preconditioning prevents murine Plasmodium infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine Plasmodium infection, focusing on CD11b high F4/80 low liver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs of Plasmodium yoelii 17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce TNF secretions, only delaying the peak of plasma IFN-γ after Plasmodium infection in mice. An in vitro phagocytic clearance assay of pRBCs showed that the CD11b high F4/80 low liver macrophages, but not spleen macrophages, in the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11b high F4/80 low liver macrophages from LPS-preconditioned mice to control mice significantly improved the survival after Plasmodium infection. We conclude that LPS preconditioning stimulated CD11b high F4/80 low liver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against Plasmodium infection.

2020 ◽  
Author(s):  
Takeshi Ono ◽  
Yoko Yamaguchi ◽  
Hiroyuki Nakashima ◽  
Masahiro Nakashima ◽  
Takuya Ishikiriyama ◽  
...  

AbstractMalaria remains a grave concern for humans, as effective medical countermeasures for malaria infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against malaria infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, how LPS preconditioning prevents murine malaria infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine malaria infection, focusing on CD11bhigh F4/80low liver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs of Plasmodium yoelii 17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce TNF secretions, only delaying the peak of plasma IFN-γ after malaria infection in mice. An in vitro phagocytic clearance assay of pRBCs showed that the CD11bhigh F4/80low liver macrophages of the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11bhigh F4/80low liver macrophages from LPS-preconditioned mice to control mice significantly improved the survival after malaria infection. We conclude that LPS preconditioning stimulated CD11bhigh F4/80low liver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against malaria infection. LPS preconditioning may be an effective tool for preventing malaria infection.


2019 ◽  
Vol 11 (3) ◽  
pp. 237-243 ◽  
Author(s):  
Montree Tungjai ◽  
Jetchada Sopapang ◽  
Natdanai Tasri ◽  
Chanatip Osothsongkroh ◽  
Attapon Jantarato ◽  
...  

2003 ◽  
Vol 47 (8) ◽  
pp. 2636-2639 ◽  
Author(s):  
Nassira Mahmoudi ◽  
Liliane Ciceron ◽  
Jean-François Franetich ◽  
Khemais Farhati ◽  
Olivier Silvie ◽  
...  

ABSTRACT The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cells. This inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. Grepafloxacin, trovafloxacin, and ciprofloxacin were the most effective drugs, with 50% inhibitory concentrations of <10 μg/ml against both strains. Only grepafloxacin, piromidic acid, and trovafloxacin had an inhibitory effect against hepatic stages of P. falciparum and P. yoelii yoelii; this effect combined reductions of the numbers and the sizes of schizonts in treated cultures. Thus, quinolones have a potential for treatment or prevention of malaria through their unique antiparasitic effect against erythrocytic and hepatic stages of Plasmodium.


2014 ◽  
Vol 82 (6) ◽  
pp. 2532-2541 ◽  
Author(s):  
S. Huang ◽  
A. Amaladoss ◽  
M. Liu ◽  
H. Chen ◽  
R. Zhang ◽  
...  

2021 ◽  
Author(s):  
Till S. Harter ◽  
Alexander M. Clifford ◽  
Martin Tresguerres

AbstractWhite seabass (Atractoscion nobilis) are increasingly experiencing periods of low oxygen (O2; hypoxia) and high carbon dioxide (CO2, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Haemoglobin (Hb) is the principal O2 carrier in the blood and in many teleost fishes Hb-O2 binding is compromised at low pH. However, Hb is contained within red blood cells (RBC) that, in some species, regulate intracellular pH with adrenergically-stimulated sodium-proton-exchangers (β-NHE). We hypothesised that white seabass have RBC β-NHEs that protect the blood O2-carrying capacity during hypoxia and hypercapnia. In a series of in vitro experiments, we determined the O2-binding characteristics of white seabass blood, the response of RBCs to adrenergic stimulation, and quantified the protective effect of β-NHE activity on Hb-O2 saturation during a hypercapnic acidosis in normoxia and hypoxia. White seabass had typical teleost Hb characteristics, with a moderate O2 affinity that was highly pH-sensitive. Functional, molecular and bioinformatic data confirmed that white seabass have RBC β-NHEs, and super-resolution imaging revealed, for the first time, the subcellular location of β-NHE protein in intracellular vesicles and on the RBC membrane. The activation of RBC β-NHEs increased Hb-O2 saturation by ∼8% in normoxia at 1% PCO2, and by ∼20% in hypoxia at arterial PCO2 (0.3%), but the protective effects decreased at higher PCO2. Combined, these data indicate that RBC β-NHE activity in white seabass can safeguard arterial O2 transport and the mechanism likely plays an important role in the fishes’ physiological response to environmental hypoxia and hypercapnia.Summary StatementWhite seabass have highly pH-sensitive haemoglobins, but their red blood cells can actively protect oxygen transport during hypoxia and hypercapnia, conditions that occur more frequently due to a changing climate.


2018 ◽  
Vol 1 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Sudeshna Paul ◽  
Shamreen Naaz ◽  
Arnab Kumar Ghosh ◽  
Sanatan Mishra ◽  
Aindrila Chattopadhyay ◽  
...  

Oxidative stress is an important causative factor for a number of diseases. Phenylhydrazine (PHZ) is a widely accepted model for studying hemolytic anemia by induction of oxidative stress. In the present study, goat red blood cells (RBCs) were incubated in vitro with PHZ (1mM) to generate oxidative stress. To test whether melatonin exhibits protective effects on PHZ induced RBC damage and to explore its potential molecular mechanisms, different concentrations of melatonin (5, 10, 20 and 40 nmoles/ml) were also included. PHZ caused altered profiles on biomarkers of oxidative stress and antioxidative as well as glucose metabolic enzymes in RBCs. These alterations indicated a development of oxidative stress. Melatonin at a concentration of 40 nmoles/ml provided optimal protection against all alterations induced by PHZ. The important cellular membrane proteins, including spectrin and actin, were also damaged by PHZ and this led to RBC deformation similar to that of observed in severe β-thalassaemia; the RBC deformation was also prevented by melatonin. Binding profiles of melatonin with PHZ and ferrous iron indicated favorable binding of melatonin with both of them, respectively. Thus, in addition to the direct antioxidant and free radical scavenging capability, melatonin also inhibited iron overloading by chelating iron and binding with the PHZ. This action of melatonin further reduces free radical generation. Based on the results, melatonin may provide therapeutic relevance to ß-thalassemia and other hemolytic RBC disorders involving oxidative stress. 


2021 ◽  
Author(s):  
Benjamaporn Supawat ◽  
Watcharit Vorasiripreecha ◽  
Sakornniya Wattanapongpitak ◽  
Suchart Kothan ◽  
Montree Tungjai

Abstract This current study was to determine the effects of in vitro exposure to radioactive cesium-137 on some human blood components (Plasma and red blood cells). Blood samples were given a radiation dose of 0.02, 0.05, 0.1, 0.2, and 0.3 mGy of gamma rays using a 137Cs radioactive standard source. The blood samples that were exposed to 0 mGy served as sham-controls. The spectrofluoroscopic technique was used to determine the autofluorescence spectrum of protein in plasma or red blood cells by using excitation wavelength and range of emission wavelengths at 280 nm and 300-550 nm, respectively. The spectrophotometric technique was used to determine the release of hemoglobin from the red blood cells to the supernatant. This data indicated no change in the ratio of fluorescence emission intensity at 340 nm of wavelength of protein extract from irradiated whole blood or red blood cells compared to the corresponding non-irradiated control. The results did not change in the absorption intensity at 415 nm of wavelength of hemoglobin leakage from in vitro irradiated red blood cells when compared to the corresponding non-irradiated red blood cells. These current results suggested that there were no harmful effects of the low-dose gamma rays from radioactive 137Cs on some blood components when human whole blood was exposed to gamma rays in an in vitro condition.


Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).


2013 ◽  
Vol 1 (Suppl. 1) ◽  
pp. A4.1
Author(s):  
Angela Storka
Keyword(s):  

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