| First Author | Piguet PF | Year | 2001 |
| Journal | Am J Pathol | Volume | 159 |
| Issue | 2 | Pages | 733-42 |
| PubMed ID | 11485931 | Mgi Jnum | J:70869 |
| Mgi Id | MGI:2148408 | Doi | 10.1016/s0002-9440(10)61744-0 |
| Citation | Piguet PF, et al. (2001) Role of CD40-CVD40L in mouse severe malaria. Am J Pathol 159(2):733-42 |
| abstractText | 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. |
