RGD Reference Report - Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. - Rat Genome Database

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Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria.

Authors: Engwerda, CR  Mynott, TL  Sawhney, S  De Souza, JB  Bickle, QD  Kaye, PM 
Citation: Engwerda CR, etal., J Exp Med. 2002 May 20;195(10):1371-7.
RGD ID: 10449455
Pubmed: PMID:12021316   (View Abstract at PubMed)
PMCID: PMC2193758   (View Article at PubMed Central)

Cerebral malaria (CM) causes death in children and nonimmune adults. TNF-alpha has been thought to play a key role in the development of CM. In contrast, the role of the related cyto-kine lymphotoxin alpha (LTalpha) in CM has been overlooked. Here we show that LTalpha, not TNFalpha, is the principal mediator of murine CM. Mice deficient in TNFalpha (B6.TNFalpha-/-) were as susceptible to CM caused by Plasmodium berghei (ANKA) as C57BL/6 mice, and died 6 to 8 d after infection after developing neurological signs of CM, associated with perivascular brain hemorrhage. Significantly, the development of CM in B6.TNFalpha-/- mice was not associated with increased intracellular adhesion molecule (ICAM)-1 expression on cerebral vasculature and the intraluminal accumulation of complement receptor 3 (CR3)-positive leukocytes was moderate. In contrast, mice deficient in LTalpha (B6.LTalpha-/-) were completely resistant to CM and died 11 to 14 d after infection with severe anemia and hyperparasitemia. No difference in blood parasite burden was found between C57BL/6, B6.TNFalpha-/-, and B6.LTalpha-/- mice at the onset of CM symptoms in the two susceptible strains. In addition, studies in bone marrow (BM) chimeric mice showed the persistence of cerebral LTalpha mRNA after irradiation and engraftment of LTalpha-deficient BM, indicating that LTalpha originated from a radiation-resistant cell population.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LTAHumancerebral malaria  ISOLta (Mus musculus) RGD 
LtaRatcerebral malaria  ISOLta (Mus musculus) RGD 
LtaMousecerebral malaria  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lta  (lymphotoxin alpha)

Genes (Mus musculus)
Lta  (lymphotoxin A)

Genes (Homo sapiens)
LTA  (lymphotoxin alpha)


Additional Information