Modulation of adhesion molecules by cytokines in vivo using human/severe combined immunodeficient (SCID) mouse chimeras

Joseph M. Pilewski, Horng Chin Yan, I. Juhász, Melpo Christofidou-Solomidou, John Williams, George F. Murphy, Steven M. Albelda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Endothelial cell-leukocyte interactions involve multiple cell adhesion molecules acting in a programmed and sequential manner to create a leukocyte-endothelial cell adhesion cascade. To understand this process fully, in vivo models are needed. To accomplish this, we have transplanted pieces of normal human tissues onto immunodeficient mice to create chimeric animals. In one model, human skin is grafted and closely resembles normal skin histologically. The grafts retain their human vasculature and show low baseline expression of E-selectin, vascular cell adhesion molecule-1, and intercellular cell adhesion molecule-1. After intradermal injection of human cytokines, these cell adhesion molecules are markedly upregulated and an active inflammatory reaction ensues, with migration of murine leukocytes. Intravenous injection of an antihuman E-selectin antibody completely inhibits leukocyte accumulation induced by tumor necrosis factor-α but only partially inhibits leukotriene B4-induced inflammation. In a second model, human bronchus was successfully transplanted heterotopically into severe combined immunodeficient mice. Injection of tumor necrosis factor induced upregulation of E-selectin, intercellular cell adhesion molecule-1, and vascular cell adhesion molecule-1 in the submucosal microvessels, with slightly different kinetics than in the skin. In conclusion, human-severe combined immunodeficient chimeric mice represent a useful model system to study the regulation and function of human cell adhesion molecules in an in vivo setting.

Original languageEnglish
JournalJournal of Clinical Immunology
Volume15
Issue number6 Supplement
DOIs
Publication statusPublished - Nov 1995

Fingerprint

SCID Mice
Cell Adhesion Molecules
Cytokines
E-Selectin
Leukocytes
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Skin
Endothelial Cells
Tumor Necrosis Factor-alpha
Intradermal Injections
Leukotriene B4
Bronchi
Microvessels
Cell Adhesion
Intravenous Injections
Cell Communication
Up-Regulation
Inflammation
Transplants

Keywords

  • Cell adhesion molecules
  • cytokines
  • inflammation
  • mouse models
  • severe combined immunodeficient (SCID) mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Pilewski, J. M., Yan, H. C., Juhász, I., Christofidou-Solomidou, M., Williams, J., Murphy, G. F., & Albelda, S. M. (1995). Modulation of adhesion molecules by cytokines in vivo using human/severe combined immunodeficient (SCID) mouse chimeras. Journal of Clinical Immunology, 15(6 Supplement). https://doi.org/10.1007/BF01540902

Modulation of adhesion molecules by cytokines in vivo using human/severe combined immunodeficient (SCID) mouse chimeras. / Pilewski, Joseph M.; Yan, Horng Chin; Juhász, I.; Christofidou-Solomidou, Melpo; Williams, John; Murphy, George F.; Albelda, Steven M.

In: Journal of Clinical Immunology, Vol. 15, No. 6 Supplement, 11.1995.

Research output: Contribution to journalArticle

Pilewski, Joseph M. ; Yan, Horng Chin ; Juhász, I. ; Christofidou-Solomidou, Melpo ; Williams, John ; Murphy, George F. ; Albelda, Steven M. / Modulation of adhesion molecules by cytokines in vivo using human/severe combined immunodeficient (SCID) mouse chimeras. In: Journal of Clinical Immunology. 1995 ; Vol. 15, No. 6 Supplement.
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