Effect of Fatty Acid Treatment in Cerebral Malaria-Susceptible and Nonsusceptible Strains of Mice

Autor: Marc Gentilini, Mohamed Moumaris, A. Halbreich, F. Miltgen, D. Sabolovic, C. Sestier
Rok vydání: 1995
Předmět:
Zdroj: The Journal of Parasitology. 81:997
ISSN: 0022-3395
DOI: 10.2307/3284055
Popis: Cerebral malaria-susceptible (C57BL/6) mice infected with Plasmodium berghei ANKA (PbA) developed low par- asitemia and died from typical neurological symptoms between 8 to 10 days after infection. In contrast, nonsusceptible (BALB/ c) mice developed high peripheral blood parasitemia and died 22-24 days later without neurological implications. Daily injections of fatty acids (FA) during the first 3 days after infection protected C57BL/6 mice from cerebral symptoms but had no effect on BALB/c mice. Thus, treated C57BL/6 mice developed hyperparasitemia and died 25 days after infection, like BALB/c mice. Red blood cells from C57BL/6 control mice were found to be more resistant to lysis by linoleic acid than those of BALB/c mice. Three days following infection with PbA, these differences disappeared. Treatment with FA prevented these changes. We concluded that the host's cells were altered soon after infection and that the nature and degree of alterations depended on the mouse strain, thus determining the eventual outcome of the infection. Likewise, the effects of FA might not be directed against the parasite but rather seem to act early after infection on these parasite-induced modifications of host cells. Cerebral malaria (CM) is frequent in certain mouse strains (C57BL/6 and CBA) and absent in others, i.e., BALB/c (Neill and Hunt, 1992). The mechanisms of cerebral disease in existing murine models are still a subject of controversy; host factors (cytokines) and parasite-derived factors (toxins) have been con- sidered to act in the capillary beds of various tissues. Also, sequestration and cytoadherence of white blood cells (murine model) or infected red blood cells (RBC; human model) are believed to have a determining role in the pathophysiology of the disease (MacPherson et al., 1985; Hommel, 1993). Recently, we reported that RBC were altered soon after in- fection, well before the RBC were actually parasitized, and de- veloped a model to study the modifications induced in biological membranes by the growing parasite. The major modification of RBC observed at this early stage was an increase of their fragility in an unsaturated linoleic acid (LNA) lysis test (Sabolovic et al., 1994). It is well documented that fatty acids (FA) are of crucial importance in the functions and properties of both host and parasite cell membranes, i.e., membrane fluidity, agglutinabil- ity, and adhesiveness, as well as in several crucial cell functions such as ion transport and receptor activity (Stubbs and Smith
Databáze: OpenAIRE