Glial cell influence on the human blood-brain barrier

Abstract

The blood-brain barrier (BBB) is a specialized structure of the central nervous system (CNS) that restricts immune cell migration and soluble molecule diffusion from the systemic compartment into the CNS. Astrocytes and microglia 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 soluble factors produced by glial cells, under basal culture conditions, help 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 phenotype of endothelial cells. These factors also induce tight junction formation between brain endothelial cells, contributing to the restricted permeability of the BBB. In contrast, these factors have little effect on expression of molecules by ECs that either promote lymphocyte migration, such as chemokines 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 system or generated within the CNS, produce an array of inflammatory molecules that increase permeability and promote lymphocyte trafficking and persistence. These observations emphasize the bidirectional nature of neural-immune interactions; this dynamic system should be amenable to therapeutic interventions.