Lymphoid B cells induce NF-kappaB activation in high endothelial cells from human tonsils.
Immune surveillance depends on still poorly understood lymphocyte-endothelium interactions required for lymphocyte transendothelial migration into secondary lymphoid organs. The nuclear factor kappaB (NF-kappaB) regulatory system and its inhibitory IkappaB proteins control the inducible expression of adhesion molecules, cytokines and chemokines involved in endothelial activation and lymphocyte transmigration. Here we present results showing the activation of this system in response to the interaction of high endothelial cells from human tonsils (HUTEC) with human B and T lymphoid cell lines and primary tonsillar lymphocytes. Western blot and electrophoretic mobility shift assays show that adhesion of different lymphoid cells induce varying levels of NF-kappaB activation in HUTEC, with Daudi cells, tonsil-derived B cell line 10 (TBCL-10) and primary tonsillar B lymphocytes causing the strongest activation. The main NF-kappaB protein complexes translocated to the nucleus were p65/p50 and p50/p50. Results from reverse transcription-PCR and flow cytometry analysis of HUTEC indicate that the interaction with Daudi cells induce an increased expression of IL-6 and IL-8 mRNA and cell-surface expression of intercellular adhesion molecule-1, all of which were prevented by sodium salicylate, an inhibitor of NF-kappaB activation. Transwell experiments show that NF-kappaB activation and the response of HUTEC to the interaction of Daudi cells does not depend on direct cell-cell contact but rather on the production of soluble factors that require the presence of both cell types. These results suggest that lymphocytes and high endothelium establish a cross talk leading to NF-kappaB-mediated expression of cytokines and adhesion molecules, inducing endothelial cell activation.
Naves
Rodrigo
R
Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Casilla, Santiago 1365, Chile.
Reyes
Lilian I
LI
Rosemblatt
Mario
M
Jacobelli
Sergio
S
González
Alfonso
A
Bono
María R
MR
D001402:B-Lymphocytes / Q000502:physiology*; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1