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PMID: 11485931 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of CD40-CVD40L in mouse severe malaria.

The American journal of pathology ·Vol. 159 ·No. 2 ·2001-08-00 ·Pages 733-42

Piguet PF, Kan CD, Vesin C, Rochat A, Donati Y, Barazzone C

Abstract

We explored the role of CD40-CD40L (CD154) in the severe malaria elicited by Plasmodium berghei anka infection in mice. Mortality was >90% by day 8 after infection in +/+ mice, but markedly decreased in CD40-/- or in CD40L-/- mice, as well as in +/+ mice treated with anti-CD40L monoclonal antibody. Parasitemia was similar in the different conditions. Breakdown of the blood-brain barrier was evident in infected +/+, but not in CD40-/- mice. Thrombocytopenia was less severe in CD40-/- mice than in the +/+ controls. Sequestration of macrophages in brain venules and alveolar capillaries was reduced in CD40-/- or in CD40L-/- mice, whereas sequestration of parasitized red blood cells or polymorphonuclear leukocytes in alveolar capillaries was CD40-CD40L-independent. CD40 mRNA was increased in the brain and lung of infected mice whereas CD40L was increased in the lung. Tumor necrosis factor plasma levels were similarly increased in infected +/+ or CD40-/- mice. Expression of CD54 and its mRNA levels in the brain were moderately decreased in CD40-deficient mice. Thus the mortality associated with severe malaria requires CD40-CD40L interaction that contributes to the breakdown of the blood-brain barrier, macrophage sequestration, and platelet consumption.

MeSH Terms
Animals Blood-Brain Barrier Brain/immunology,pathology CD40 Antigens/genetics,physiology CD40 Ligand/genetics,physiology Gene Expression Regulation/immunology Intercellular Adhesion Molecule-1/genetics Macrophages/physiology Malaria/blood,immunology,pathology Mice Mice, Inbred C57BL Mice, Knockout Plasmodium berghei Platelet Count RNA, Messenger/genetics Thrombocytopenia Transcription, Genetic Tumor Necrosis Factor-alpha/metabolism
Chemicals
CD40 Antigens RNA, Messenger Tumor Necrosis Factor-alpha Intercellular Adhesion Molecule-1 CD40 Ligand
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Piguet P F
Department of Pathology, University of Geneva, 1 rue M. Servet, CMU, 1211 Geneva, Switzerland. [email protected]
Kan C D
Vesin C
Rochat A
Donati Y
Barazzone C
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/s0002-9440(10)61744-0
Email
[email protected]
Published
2001-08-00
Pages
733-42
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1850550
Subset
IM
External Links
PubMed source DOI: 10.1016/s0002-9440(10)61744-0 PMC Full Text View journal details
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