Comparison of E-selectin expression at mRNA and protein levels in murine models of inflammation

SA Asgeirsdottir, RJ Kok, J Twisk, B de Vries, E Lubberts, EJ Bos, N Werner, DKF Meijer, G Molema*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Background: Drug targeting to activated endothelial cells via E-selectin is currently being explored as a new approach to treat chronic inflammatory disorders. This approach uses E-selectin directed antibodies as carrier molecules to selectively deliver anti-inflammatory drugs into activated endothelial cells, thereby theoretically decreasing drug-associated side-effects. Therapeutic effects of developed drug targeting constructs will have to be tested in animal models of inflammation, in which E-selectin is expressed during the course of the disease. In this study several murine models of inflammation were investigated regarding expression of E-selectin.

Methods: E-selectin expression was determined both at the mRNA level using RT-PCR and at the protein level by immunohistochemistry using two monoclonal antibodies (10E9.6 and MES-1). The models studied included delayed type hypersensitivity induced skin inflammation, dextran sodium sulphate induced colitis, kidney ischemia/reperfusion injury, atherosclerosis in ApoE knockout mice, and collagen induced arthritis.

Results: In all animal models E-selectin mRNA expression was detected, although to a different extent. In contrast, only the delayed type hypersensitivity model and, to a minor extent, the collagen induced arthritis model showed E-selectin protein expression.

Conclusions: These results stress the need to determine E-selectin protein expression and not only mRNA expression, when choosing an animal model for testing E-selectin directed drug targeting preparations. In addition, in the arthritis model, E-selectin protein detection was dependent on the particular anti-E-selectin antibody used. This finding may not only have implications for the development and/or choice of homing devices to be used in E-selectin directed drug targeting preparations, but also for inflammation research in general.

Original languageEnglish
Pages (from-to)512-518
Number of pages7
JournalInflammation research
Volume52
Issue number12
DOIs
Publication statusPublished - Dec-2003

Keywords

  • inflammation
  • animal models
  • E-selectin
  • immunohistochemistry
  • RT-PCR
  • INTERCELLULAR-ADHESION MOLECULE-1
  • ACTIVATED ENDOTHELIAL-CELLS
  • RENAL ISCHEMIA-REPERFUSION
  • SOLUBLE E-SELECTIN
  • P-SELECTIN
  • IN-VIVO
  • DELIVERY
  • MICE
  • IMMUNOCONJUGATE
  • DEXAMETHASONE

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