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PMID: 12707049 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anti-adhesive effect of nitric oxide on Plasmodium falciparum cytoadherence under flow.

The American journal of pathology ·Vol. 162 ·No. 5 ·2003-05-00 ·Pages 1651-60

Serirom S, Raharjo WH, Chotivanich K, Loareesuwan S, Kubes P, Ho M

Abstract

Nitric oxide (NO) is widely known to inhibit platelet and leukocyte adhesion to endothelium through its regulatory effect on adhesion molecule expression. The objective of the present study was to investigate if NO affects the cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBCs) to human microvascular endothelium (HDMECs) under flow conditions in vitro. The effect of endogenous NO was studied using the NO synthase inhibitor L-N(G)-nitro-arginine-methyl-ester (L-NAME). Treatment of HDMECs with 3 mmol/L of L-NAME for 4 hours significantly enhanced IRBC adhesion and the effect could be reversed by an anti-P-selectin but not an anti-VCAM-1 antibody. The effect of exogenous NO on cytoadherence was studied by using the NO donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PPN). PPN (300 micro mol/L) treatment reduced the number of adherent IRBCs on resting HDMECs by down-regulating basal ICAM-1 expression, and on tumor necrosis factor-alpha-stimulated HDMECs by inhibition of VCAM-1 induction and down-regulation of ICAM-1 expression. The inhibitory effect of PPN on tumor necrosis factor-alpha-induced VCAM-1 expression at 24 hours was evident when the NO donor was added for as short as 2 hours. These findings suggest that NO may be protective against P. falciparum infection by inhibiting cytoadherence, and underscore the therapeutic potential of NO in the treatment of severe falciparum malaria.

MeSH Terms
Adult Animals Base Sequence Cell Adhesion/drug effects,physiology DNA Primers Endothelium, Vascular/parasitology,physiology Erythrocytes/drug effects,parasitology,physiology Humans In Vitro Techniques Kinetics Malaria, Falciparum/blood NG-Nitroarginine Methyl Ester/pharmacology Nitric Oxide/physiology Nitric Oxide Donors/pharmacology P-Selectin/genetics Plasmodium falciparum/drug effects,physiology Polymerase Chain Reaction RNA, Messenger/genetics
Chemicals
DNA Primers Nitric Oxide Donors P-Selectin RNA, Messenger Nitric Oxide NG-Nitroarginine Methyl Ester
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Serirom Supattra
Department of Microbiology and Infectious Diseases and Immunology Research Group, University of Calgary, Calgary, Alberta, Canada.
Raharjo Wahaju H
Chotivanich Kesinee
Loareesuwan Sornchai
Kubes Paul
Ho May
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
2003-05-00
Pages
1651-60
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1851209
Subset
IM
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