ABO blood antigens define human cerebral endothelial diversity

Cerebral endothelial cells participate in the blood-brain barrier and regulate activity-dependent changes in brain blood flow. It has been assumed that all cerebral endothelial cells are similar, but genetic studies in mice suggest that there are heterogeneous populations of endothelial cells in rodent brain. In this study, we tested for molecular heterogeneity of endothelial cells in the human brain. Human brains (five A and five O blood type patients) from autopsies were analyzed by immunohistochemistry and immunofluorescence using antibodies against von Willebrand factor (vWF) and A and H blood group antigens. vWF and ABO antigens were confined to the endothelium. Although all endothelial cells expressed vWF, capillary endothelial cells from A blood type brains showed a heterogeneous expression of A and H antigens, with individual cells expressing either one or both antigens. There were no differences between the gray and the white matter in the percentage of A-reactive or H-reactive capillaries. We conclude that ABO antigen expression in the human brain is modulated at the level of the individual endothelial cell. Future studies are warranted to determine whether differences in capillary permeability and cerebral autoregulation vary over short distances within the brain.