Lesion associated expression of urokinase-type plasminogen activator receptor (uPAR, CD87) in human cerebral malaria

Blood-brain barrier disintegration and inflammatory cell recruitment are ke y processes in the pathogenesis of cerebral malaria (CM). Recent data provi de convincing evidence that the serine protease urokinase-type plasminogen activator receptor (uPAR) is a key molecule in promoting cell adhesion and spreading. We have now analyzed expression of urokinase-type plasminogen ac tivator receptor (uPAR, CD87), which is part of a cell surface associated p roteolytic system, in brains of eight CM patients and seven neuropathologic ally unaltered and diseased controls by immunohistochemistry. Double labeli ng experiments with antibodies directed against CD68 (macrophages/microglia l cells), myeloid-related protein (MRP8), and glial fibrillary acid protein (GFAP) confirmed the nature of uPAR expressing cells. We observed focal ac cumulation of uPAR expressing macrophages/microglial cells in Durck's granu lomas and adjacent to petechial hemorrhages, in astrocytes, and in endothel ial cells. In contrast, focal uPAR expression in macrophages/microglial cel ls but not in astrocytes was found in microglial nodules of toxoplasmic enc ephalitis and in the cellular infiltrate of bacterial meningitis. Normal br ains showed only faint uPAR expression in endothelial cells. We conclude fr om these data that lesion-associated uPAR expression at least in part contr ibutes to blood-brain barrier alteration and immunologic dysfunction in CM patients. (C) 2000 Elsevier Science BN. All rights reserved.