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CD156 transgenic mice. Different responses between inflammatory types.

Yasunori Higuchi1, Atsushi Yasui, Keiko Matsuura

  • 1Department of Pathology, Oita Medical University, Oita, Japan. higuchi@oita-med.ac.jp

Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology
|November 5, 2002
PubMed
Summary

Transgenic mice expressing CD156 (ADAM8) ectodomain showed altered leukocyte infiltration. Soluble CD156 (sCD156) reduced leukocyte infiltration but enhanced contact hypersensitivity, suggesting complex roles in immune responses.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • CD156 (ADAM8) is a metalloprotease-disintegrin protein involved in various biological processes.
  • The specific in vivo functions of CD156, particularly its soluble form, remain incompletely understood.

Purpose of the Study:

  • To investigate the in vivo role of CD156 by generating transgenic mice expressing its ectodomain.
  • To elucidate the impact of soluble CD156 (sCD156) on leukocyte infiltration and inflammatory responses.

Main Methods:

  • Generation of transgenic mice (ATMS2-TG18) expressing CD156 ectodomain under the alpha1-antitrypsin promoter.
  • Analysis of CD156 mRNA expression in response to turpentine oil (TO) and lipopolysaccharide (LPS).
  • Assessment of leukocyte infiltration (casein-induced) and contact hypersensitivity reactions (oxazolone-induced) in transgenic and non-transgenic mice.

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Main Results:

  • Transgenic mice exhibited constitutive production of sCD156, which increased upon TO treatment.
  • Casein-induced leukocyte infiltration was significantly reduced in transgenic mice.
  • Contact hypersensitivity reactions were enhanced in transgenic mice, with detected E-selectin mRNA expression in inflammatory skin sites.
  • L-selectin expression on neutrophils was downregulated in transgenic mice, suggesting shedding mediated by sCD156.

Conclusions:

  • Soluble CD156 (sCD156) plays a dual role in regulating leukocyte infiltration, inhibiting general infiltration while potentially promoting specific inflammatory responses.
  • sCD156 may shed L-selectin from neutrophils and activate endothelial cells, leading to E-selectin upregulation.
  • CD156 is a key regulator of leukocyte trafficking and inflammatory processes.