Blood–Brain Barrier Pericytes Are the Main Source of γ‐Glutamyltranspeptidase Activity in Brain Capillaries

Abstract

Cerebral endothelial cells form the selective permeability barrier between brain and blood by virtue of their impermeable tight junctions and the presence of specific carrier systems. These specialized properties of brain capillaries are reflected in the presence of proteins that are not found in other capillaries of the body. gamma-Glutamyltranspeptidase (GGT) has been widely used as a marker for brain capillaries and differentiated properties of brain endothelial cells. By using histochemical and biochemical methods we have investigated the expression of GGT in isolated capillaries, cultured brain endothelial cells and pericytes, and cocultures of astrocytes and brain endothelial cells. It was surprising that the majority of GGT activity was associated with pericytes, but not endothelial cells, suggesting that GGT is a specific marker for brain pericytes. The remaining GGT activity that was associated with endothelial cells rapidly disappeared from cultured cells but was reinduced in cocultures with astrocytes. Our results emphasize the need for pure endothelial cells for the investigation of blood-brain barrier characteristics.

Isolation of Endothelial Cells from Brain, Lung, and Kidney: Expression of the Multidrug Resistance P-Glycoprotein Isoforms

“…For brain tissue, our results suggest that ␥-GT is not mainly expressed by EC. This is in agreement with the results of Risau et al (26) showing that pericytes are the main source of ␥-GT activity in brain capillaries. These results also indicate that the cells isolated from the three tissues are not contaminated by pericytes or by kidney and lung epithelial cells since these types of cells are known to express high levels of ␥-GT (27,28).…”

Differences between the Pathogenesis of Senile Plaques and Congophilic Angiopathy in Alzheimer Disease

“…The impact of CA in AD brains may extend beyond vascular pathology only. Endothelial cells and, to a lesser extent, pericytes, are involved in maintaining the blood-brain barrier (87). Degeneration of these cells in vessels affected by CA may lead to an impaired functioning of the blood-brain barrier in AD patients, which contributes to a disrupted microcirculation and energy supply to the brain (88), which, in turn, will have profound effects on brain me tabolism in general.…”

Role of the CNS microvascular pericyte in the blood-brain barrier

“…They undergo remarkable vascular changes and exhibit increased vesicular and tubular transport (Glees et al 1989). In addition, pericyte expression of enzymes such as ␥-glutamyltranspeptidase (Risau et al, 1992), glutamyl aminopeptidase (Hearly and Wilk, 1993), aminopeptidase N (Kunz et al, 1994), glutamic acid decarboxylase (Gradera et al, 1993), and butyrylcholinesterase (Gerhart et al, 1987) highlight the enzymatic and metabolic aspects of their barrier function. Pericytes play an important hemostatic role in the initiation and the propagation of the coagulant response through the extrinsic pathway.…”