Role of ICAM-1 (CD54) in the development of murine cerebral malaria

In susceptible mouse strains, infection of mice with Plasmodium berghei ANK A (PbA) results in a lethal complication, cerebral malaria. Cerebral malari a is due to the immune response induced by the parasite, which result-a in an increased production of TNF, known to increase the expression of adhesio n molecules on the endothelia. To investigate the role of the adhesion mole cule ICAM-1 (CD54), we infected wild-type (+/+) and ICAM-1-deficient (-/-) mice with PbA. While +/+ mice died 6-8 days after infection, -/- mice survi ved > 15 days. Parasitaemia was similar in +/+ and -/- mice. Serum TNF conc entration was increased by the infection and was significantly higher in in fected +/+ than in -/- mice, However, TNF mRNA levels in spleen, lungs, and brain were elevated in both infected +/+ and -/- mice, For IFN-gamma, seru m levels were similar in both groups. A breakdown of the blood-brain barrie r was evident in infected +/+ mice only. Interestingly, thrombocytopenia wa s profound in infected +/+, but practically absent in -/- mice, Moreover, m acrophage sequestration was evident in brain venules and lung capillaries o f +/+ mice and was significantly less important in the alveolar capillaries of infected -/- mice. In contrast, neutrophil sequestration in the lung wa s similar in both +/+ and -/- mice. Sequestration of parasitized red blood cells was significantly greater in the alveolar capillaries from +/+ than - /- mice. These results indicate that while the immune response is similar i n both +/+ and ICAM-1(-/-) mice, the absence of mortality in ICAM(-/-) mice correlates with a decrease of macrophage and parasitized RBC trapping and a less severe thrombocytopenia. (C) 1999 Editions sciencifiques et medicale s Elsevier SAS.