Abstract
Cerebral malaria (CM) is a severe clinical complication of Plasmodium falciparum malaria infection and is characterized by a high fatality rate and neurological damage. Sequestration of parasite-infected red blood cells in brain microvasculature utilizes host- and parasite-derived adhesion molecules and is an important factor in the development of CM. ICAM-1, an alternatively spliced adhesion molecule, is believed to be critical on endothelial cells for infected red blood cell sequestration in CM. Using ICAM-1 mutant mice, we found that the full-length ICAM-1 isoform is not required for development of murine experimental CM (ECM) and that ECM phenotype varies with the combination of ICAM-1 isoforms expressed. Furthermore, we observed development of ECM in transgenic mice expressing ICAM-1 only on leukocytes, indicating that endothelial cell expression of this adhesion molecule is not required for disease pathogenesis. We propose that ICAM-1-dependent cellular aggregation, independent of ICAM-1 expression on the cerebral microvasculature, contributes to ECM.
Highlights
Endothelium-expressed intercellular adhesion molecule-1 (ICAM-1) is considered critical for the development of cerebral malaria (CM)
Using ICAM-1 mutant mice, we found that the full-length ICAM-1 isoform is not required for development of murine experimental Cerebral malaria (CM) (ECM) and that ECM phenotype varies with the combination of ICAM-1 isoforms expressed
We report the unexpected finding that ICAM-1 expression on central nervous system (CNS) microvasculature is not required for ECM development
Summary
Endothelium-expressed intercellular adhesion molecule-1 (ICAM-1) is considered critical for the development of cerebral malaria (CM). We observed development of ECM in transgenic mice expressing ICAM-1 only on leukocytes, indicating that endothelial cell expression of this adhesion molecule is not required for disease pathogenesis.
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