Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria.
J Exp Med
; 195(10): 1371-7, 2002 May 20.
Article
em En
| MEDLINE
| ID: mdl-12021316
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
3_ND
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Linfotoxina-alfa
/
Fator de Necrose Tumoral alfa
/
Malária Cerebral
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2002
Tipo de documento:
Article