Glial cell influence on the human blood-brain barrier

The blood-brain barrier (BBB) is a specialized structure of the central ner vous system (CNS) that restricts immune cell migration and soluble molecule diffusion from the systemic compartment into the CNS. Astrocytes and micro glia are resident cells of the CNS that contribute to the formation of the BBB. In this article, we consider the influence of these glial cells on the immune regulatory functions of the microvascular endothelium, with special emphasis on the human BBB. A series of in vitro studies demonstrate that s oluble factors produced by glial cells, under basal culture conditions, hel p restrict development of inflammation within the CNS. These soluble factor effects include upregulating expression of molecules including HT7, UEA-1 lectin-binding sites, and angiotensin receptors that help define the phenot ype of endothelial cells. These factors also induce tight junction formatio n between brain endothelial cells, contributing to the restricted permeabil ity of the BBB. In contrast, these factors have little effect on expression of molecules by ECs that either promote lymphocyte migration, such as chem okines and adhesion molecules or molecules that are required for competent antigen presentation, such as MHC and co-stimulatory molecules. Glial cells that become activated in response to signals derived from the immune syste m or generated within the CNS, produce an array of inflammatory molecules t hat increase permeability and promote lymphocyte trafficking and persistenc e. These observations emphasize the bidirectional nature of neural-immune i nteractions; this dynamic system should. be amenable to therapeutic interve ntions. (C) 2001 Wiley-Liss, Inc.