Expression of the beta-chemokines RANTES and MIP-1 beta by human brain microvessel endothelial cells in primary culture

The mechanisms that regulate inflammatory cell recruitment across the blood -brain barrier (BBB) during CNS inflammation have not been fully characteri zed. Likely players in this process include the chemokines, small secondary messengers of inflammation capable of subset-specific leukocyte activation and chemoattraction. Primary cultures of human brain microvessel endotheli al cells (HBMEC) were examined for their in vitro expression of the beta ch emokines RANTES and MIP-le. Untreated HBMEC expressed low levels of RANTES and MIP-1 beta RNA that were significantly upregulated following cytokine t reatment. Parallel studies performed on human umbilical Vein endothelial ce lls (HUVEC) showed induction of RANTES but not MIP-1 beta RNA. Following st imulation with LPS, TNF-alpha, IFN-gamma, and IL-1 beta alone or in combina tion, HBMEC released significant amounts of RANTES and MIP-1 beta into the culture supernatants. RANTES secretion by HUVEC could be induced only with TNF-alpha/IFN-gamma. Both RANTES and MIP-1 beta were detected by immunocyto chemistry on the apical and basal surfaces of HBMEC, as well as bound to ba sal lamina-like material under the basal cell surface. Cytokine stimulation induced significant increase of RANTES and MIP-1 beta molecules associated with the EC surface and subendothelial matrix. The expression of RANTES an d MIP-1 beta by HBMEC suggests that these chemokines may play an important role in mediating inflammatory responses and leukocyte trafficking across t he BBB.