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

M. Everts, S. A. Asgeirsdottir, R. J. Kok, J. Twisk, B. de Vries, E. Lubberts, E. J. Bos, N. Werner, D. K. F. 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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