PMID:12819012

Citation	Baekkevold, ES, Roussigné, M, Yamanaka, T, Johansen, FE, Jahnsen, FL, Amalric, F, Brandtzaeg, P, Erard, M, Haraldsen, G and Girard, JP (2003) Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. Am. J. Pathol. 163:69-79
Abstract	Lymphocyte homing to secondary lymphoid tissue and lesions of chronic inflammation is directed by multi-step interactions between the circulating cells and the specialized endothelium of high endothelial venules (HEVs). In this study, we used the PCR-based method of suppression subtractive hybridization (SSH) to identify novel HEV genes by comparing freshly purified HEV endothelial cells (HEVECs) with nasal polyp-derived microvascular endothelial cells (PMECs). By this approach, we cloned the first nuclear factor preferentially expressed in HEVECs, designated nuclear factor from HEVs (NF-HEV). Virtual Northern and Western blot analyses showed strong expression of NF-HEV in HEVECs, compared to human umbilical vein endothelial cells (HUVECs) and PMECs. In situ hybridization and immunohistochemistry revealed that NF-HEV mRNA and protein are expressed at high levels and rather selectively by HEVECs in human tonsils, Peyers's patches, and lymph nodes. The NF-HEV protein was found to contain a bipartite nuclear localization signal, and was targeted to the nucleus when ectopically expressed in HUVECs and HeLa cells. Furthermore, endogenous NF-HEV was found in situ to be confined to the nucleus of tonsillar HEVECs. Finally, threading and molecular modeling studies suggested that the amino-terminal part of NF-HEV (aa 1-60) corresponds to a novel homeodomain-like Helix-Turn-Helix (HTH) DNA-binding domain. Similarly to the atypical homeodomain transcription factor Prox-1, which plays a critical role in the induction of the lymphatic endothelium phenotype, NF-HEV may be one of the key nuclear factors that controls the specialized HEV phenotype.
Links	PubMed PMC1868188 Online version:10.1016/S0002-9440(10)63631-0
Keywords	Amino Acid Sequence; Animals; Cell Line; Endothelium, Lymphatic/cytology; Endothelium, Lymphatic/physiology; Endothelium, Vascular/metabolism; Helix-Turn-Helix Motifs; Humans; In Situ Hybridization; Interleukins; Lymph Nodes/cytology; Lymph Nodes/metabolism; Lymphocytes; Mice; Models, Molecular; Molecular Sequence Data; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Nucleic Acid Hybridization/methods; Palatine Tonsil/cytology; Palatine Tonsil/metabolism; Peyer's Patches/cytology; Peyer's Patches/metabolism; Protein Structure, Tertiary; Sequence Alignment; Venules/cytology; Venules/metabolism
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.