Advertisement

High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature

  • Kevin L. Bentley
  • Sharon Stranford
  • Shan Liao
  • Rawad M. Mounzer
  • Frank H. Ruddle
  • Nancy H. Ruddle
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)

Abstract

Lymphotoxin (LT) is crucial for the regulation of HEV adhesion molecules MAdCAM-1 and PNAd and a sulfotransferase, GlcNAc6ST-2 (gene symbol Chst4); here called HEC-6ST. Following immunization, some HEVs express markers of both HEVs (PNAd) and LVs (LYVE-1). In order to evaluate this process in real time, we have developed mice transgenic for a construct that consists of an HEV specific gene driving a green fluorescent reporter gene (eGFP). These mice express the reporter gene in HEVs in concurrence with the endogenous gene and PNAd. Additional mice transgenic for lymphatic vessel reporter constructs are in development. These will provide material for in vivo imaging and allow us to evaluate the regulation and interaction of HEVs and LVs.

Keywords

Green Fluorescent Protein Reporter Mouse Afferent Lymphatic Vessel SV40 Polyadenylation Signal Mucosal Addressin Cell Adhesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

LN

lymph node

PLN

peripheral lymph node

LTβR

lymphotoxin-β receptor

LV

lymphatic vessel

HEV

high endothelial venule

PNAd

peripheral node addressin

HEC-6ST

high endothelial cell sulfotransferase, HEC-GlcNA6ST, GlcNAc6ST-2, N-acetyl glucosamine 6-O-sulfotransferase-2; carbohydrate (chondroitin 6/keratan) sulfotransferase 4

MAdCAM-1

mucosal addressin cell adhesion molecule 1

GlyCAM-1

glycosylation-dependent cell adhesion molecule-1

OX

oxazolone

LYVE-1

lymphatic vessel endothelial hyaluronan receptor 1

GFP

green fluorescent protein

L-sel

L-selectin

PROX1

prospero-related homeobox 1

Notes

Acknowledgments

We thank Myriam Hill for figure preparation and Myriam Hill and Daniel Reagan for outstanding technical assistance. This work was supported by U.S. Public Health Service Grants R01 DK057731 and CA016885 (to N.H.R.) and GM09966 (to F.H.R.) from the National Institutes of Health, a Mount Holyoke College Faculty Research Fellowship (to S.S) and a Lymphatic Research Foundation Fellowship (to R.A.M.)

References

  1. 1.
    Ruddle NH, Akirav EM (2009) Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response. J Immunol 183:2205–2212CrossRefPubMedGoogle Scholar
  2. 2.
    Mebius RE, Streeter PR, Michie S, Butcher EC, Weissman IL (1996) A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+CD3- cells to colonize lymph nodes. Proc Natl Acad Sci 93:11019–11024CrossRefPubMedGoogle Scholar
  3. 3.
    Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, Huang CC, Kannagi R, Rosen SD, Hemmerich S (1999) Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin. J Cell Biol 145:899–910CrossRefPubMedGoogle Scholar
  4. 4.
    Hiraoka N, Petryniak B, Nakayama J, Tsuboi S, Suzuki M, Yeh JC, Izawa D, Tanaka T, Miyasaka M, Lowe JB, Fukuda M (1999). A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis(x), an L-selectin ligand displayed by CD34. Immunity 11:79–89CrossRefPubMedGoogle Scholar
  5. 5.
    Cuff CA, Sacca R, Ruddle NH (1999) Differential induction of adhesion molecule and chemokine expression by LTalpha3 and LTalphabeta in inflammation elucidates potential mechanisms of mesenteric and peripheral lymph node development. J Immunol 162:5965–5972PubMedGoogle Scholar
  6. 6.
    Cuff CA, Schwartz J, Bergman CM, Russell KS, Bender JR, Ruddle NH (1998) Lymphotoxin alpha3 induces chemokines and adhesion molecules: insight into the role of LT alpha in inflammation and lymphoid organ development. J Immunol 161:6853–6860PubMedGoogle Scholar
  7. 7.
    Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH (2003) Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J Exp Med 197:1153–1163CrossRefPubMedGoogle Scholar
  8. 8.
    Kratz A, Campos-Neto A, Hanson MS, Ruddle NH (1996) Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J Exp Med 183:1461–1472CrossRefPubMedGoogle Scholar
  9. 9.
    Sacca R, Cuff CA, Lesslauer W, Ruddle NH (1998) Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J Immunol 160:485–491PubMedGoogle Scholar
  10. 10.
    Drayton DL, Bonizzi G, Ying X, Liao S, Karin M, Ruddle NH (2004) I kappaB kinase complex alpha kinase activity controls chemokine and high endothelial venule gene expression in lymph nodes and nasal-associated lymphoid tissue. J Immunol 173:6161–6168PubMedGoogle Scholar
  11. 11.
    Mounzer RM, Svendsen OS, Baluk P, Bergman CM, Padera TP, Wiig H, Jain RK, McDonald DM, Ruddle NH (2010). Lymphotoxin alpha contributes to lymphangiogenesis. Blood June 21 Epub ahead of print.Google Scholar
  12. 12.
    Liao S, Ruddle NH (2006) Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J Immunol 177:3369–3379PubMedGoogle Scholar
  13. 13.
    DeTogni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J et al (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703–707CrossRefGoogle Scholar
  14. 14.
    Koni PA, Sacca R, Lawton P, Browning JL, Ruddle NH, Flavell RA (1997) Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 6:491–500CrossRefPubMedGoogle Scholar
  15. 15.
    Liao S, Bentley K, Lebrun M, Lesslauer W, Ruddle FH, Ruddle NH (2007) Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules. Proc Natl Acad Sci USA 104:4577–4582CrossRefPubMedGoogle Scholar
  16. 16.
    Bradshaw MS, Bollekens JA, Ruddle FH (1995) A new vector for recombination-based cloning of large DNA fragments from yeast artificial chromosomes. Nucleic Acids Res 23:4850–4856CrossRefPubMedGoogle Scholar
  17. 17.
    Shashikant CS, Carr JL, Bhargava J, Bentley KL, Ruddle FH (1998) Recombinogenic targeting: a new approach to genomic analysis–a review. Gene 223:9–20CrossRefPubMedGoogle Scholar
  18. 18.
    Bistrup A, Tsay D, Shenoy P, Singer MS, Bangia N, Luther SA, Cyster JG, Ruddle NH, Rosen SD (2004) Detection of a sulfotransferase (HEC-GlcNAc6ST) in high endothelial venules of lymph nodes and in high endothelial venule-like vessels within ectopic lymphoid aggregates: relationship to the MECA-79 epitope. Am J Pathol 164:1635–1644PubMedGoogle Scholar
  19. 19.
    Oliver G (2004) Lymphatic vasculature development. Nat Rev Immunol 4:35–45CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kevin L. Bentley
    • 1
  • Sharon Stranford
    • 2
  • Shan Liao
    • 1
    • 3
  • Rawad M. Mounzer
    • 1
    • 4
  • Frank H. Ruddle
    • 5
  • Nancy H. Ruddle
    • 1
    • 6
  1. 1.Department of Epidemiology and Public HealthYale University School of MedicineNew HavenUSA
  2. 2.Department of Biological SciencesMount Holyoke CollegeSouth HadleyUSA
  3. 3.Department of Radiation OncologyE.L. Steele Laboratory for Tumor Biology, Massachusetts General HospitalBostonUSA
  4. 4.Department of Internal MedicineUPMC Montefiore HospitalPittsburghUSA
  5. 5.Department of Molecular, Cellular, and Developmental BiologyYale UniversityNew HavenUSA
  6. 6.Departments of Epidemiology and Public Health and ImmunobiologyYale University School of MedicineNew HavenUSA

Personalised recommendations