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 characterized. 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 endothelial cells (HBMEC) were examined for their in vitro expression of the beta chemokines RANTES and MIP-1beta. Untreated HBMEC expressed low levels of RANTES and MIP-1beta RNA that were significantly upregulated following cytokine treatment. Parallel studies performed on human umbilical vein endothelial cells (HUVEC) showed induction of RANTES but not MIP-1beta RNA. Following stimulation with LPS, TNF-alpha, IFN-gamma, and IL-1beta alone or in combination, HBMEC released significant amounts of RANTES and MIP-1beta into the culture supernatants. RANTES secretion by HUVEC could be induced only with TNF-alpha/IFN-gamma. Both RANTES and MIP-1beta were detected by immunocytochemistry on the apical and basal surfaces of HBMEC, as well as bound to basal lamina-like material under the basal cell surface. Cytokine stimulation induced significant increase of RANTES and MIP-1beta molecules associated with the EC surface and subendothelial matrix. The expression of RANTES and MIP-1beta by HBMEC suggests that these chemokines may play an important role in mediating inflammatory responses and leukocyte trafficking across the BBB.
Shukaliak
J A
JA
Department of Pathology and Laboratory Medicine, Vancouver General Hospital and the University of British Columbia, Canada.
Dorovini-Zis
K
K
D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000502:physiology*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D008833:Microcirculation / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger