A role for Fas-Fas ligand interactions during the late-stage neuropathological processes of experimental cerebral malaria.
Cerebral malaria (CM) kills more than 1 million children each year. Using a murine model of CM, we investigated the role of Fas-Fas ligand interactions in the neuropathogenesis of this disease. Lpr and Gld mice, deficient in Fas and Fas ligand, respectively, were protected from fatal CM, although they demonstrated some pathological features associated with CM in the wild type mouse. Fas-Fas ligand mRNA and protein expression were increased in the brain in mice with CM, and activated caspase-3-positive apoptotic astrocytes were observed. We suggest that Fas-mediated apoptosis of astrocytes is likely to be a critical factor in late-stage murine CM pathogenesis.
Potter
Sarah M
SM
Department of Pathology, Institute for Biomedical Research, University of Sydney, NSW 2006, Australia. potter@cochin.inserm.fr
Chan-Ling
Tailoi
T
Rosinova
Emilia
E
Ball
Helen J
HJ
Mitchell
Andrew J
AJ
Hunt
Nicholas H
NH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016779:Malaria, Cerebral / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D019014:fas Receptor