Document Detail


Natural hemozoin stimulates syncytiotrophoblast to secrete chemokines and recruit peripheral blood mononuclear cells.
MedLine Citation:
PMID:  21632106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Placental malaria is associated with local accumulation of parasitized erythrocytes, deposition of the parasite hemoglobin metabolite, hemozoin, and accumulation of mononuclear cells in the intervillous space. Fetal syncytiotrophoblast cells in contact with maternal blood are known to respond immunologically to cytoadherent Plasmodium falciparum-infected erythrocytes, but their responsiveness to hemozoin, a potent pro-inflammatory stimulator of monocytes, macrophages and dendritic cells, is not known.
METHODS: The biochemical and immunological changes induced in primary syncytiotrophoblast by natural hemozoin was assessed. Changes in syncytiotrophoblast mitogen-activated protein kinase activation was assessed by immunoblotting and secreted cytokine and chemokine proteins were assayed by ELISA. Chemotaxis of peripheral blood mononuclear cells was assessed using a two-chamber assay system and flow cytometry was used to assess the activation of primary monocytes by hemozoin-stimulated syncytiotrophoblast conditioned medium.
RESULTS: Hemozoin stimulation induced ERK1/2 phosphorylation. Treated cells secreted CXCL8, CCL3, CCL4, and tumor necrosis factor and released soluble intercellular adhesion molecule-1. Furthermore, the dependence of the hemozoin responses on ERK1/2 stimulation was confirmed by inhibition of chemokine release in syncytiotrophoblast treated with an ERK pathway inhibitor. Hemozoin-stimulated cells elicited the specific migration of PBMCs, and conditioned medium from the cells induced the upregulation of intercellular adhesion molecule-1 on primary monocytes.
CONCLUSIONS: These findings confirm an immunostimulatory role for hemozoin and expand the cell types known to be responsive to hemozoin to include fetal syncytiotrophoblast. The results provide further evidence that syncytiotrophoblast cells can influence the local maternal immune response to placental malaria.
Authors:
N W Lucchi; D Sarr; S O Owino; S M Mwalimu; D S Peterson; J M Moore
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-31
Journal Detail:
Title:  Placenta     Volume:  32     ISSN:  1532-3102     ISO Abbreviation:  Placenta     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-22     Completed Date:  2011-11-21     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  England    
Other Details:
Languages:  eng     Pagination:  579-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Cell Movement / drug effects
Chemokines / immunology,  secretion*
Culture Media, Conditioned / pharmacology
Female
Hemeproteins / pharmacology*
Humans
Intercellular Adhesion Molecule-1 / biosynthesis
Leukocytes, Mononuclear / immunology*
Malaria, Falciparum / blood,  immunology*
Mitogen-Activated Protein Kinases / metabolism
Plasmodium falciparum / immunology
Pregnancy
Pregnancy Complications, Parasitic / immunology*
Trophoblasts / drug effects,  immunology*
Up-Regulation
Grant Support
ID/Acronym/Agency:
R01 AI050240/AI/NIAID NIH HHS; R01 AI050240/AI/NIAID NIH HHS; R01 AI050240-01/AI/NIAID NIH HHS; R01 AI050240-02/AI/NIAID NIH HHS; R01 AI050240-03/AI/NIAID NIH HHS; R01 AI050240-04/AI/NIAID NIH HHS; R01 AI050240-05/AI/NIAID NIH HHS; R21 AI090439/AI/NIAID NIH HHS; R21 AI090439/AI/NIAID NIH HHS; R21 AI090439-01/AI/NIAID NIH HHS; R21 AI090439-02/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 0/Culture Media, Conditioned; 0/Hemeproteins; 126547-89-5/Intercellular Adhesion Molecule-1; 39404-00-7/hemozoin; EC 2.7.11.24/Mitogen-Activated Protein Kinases
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