en
Scientific article
English

Diminished lymphocyte adhesion and alleviation of allergic responses by small-molecule- or antibody-mediated inhibition of L-selectin functions

Published inJournal of investigative dermatology, vol. 127, no. 1, p. 90-97
Publication date2007
Abstract

Selectins are attractive targets for specific anti-inflammatory therapies. Using human lymphocytes as well as an L-selectin-transfected pre-B-cell line in dynamic flow chamber experiments, we could demonstrate that the small-molecule compound efomycine M blocks L-selectin-mediated lymphocyte rolling on sialylated Lewis(X), an action that was confirmed by plasmon resonance spectroscopy. Recruitment of naive lymphocytes to peripheral lymph nodes depends on L-selectin-mediated adhesion to high endothelial venules. We performed intravital microscopy studying lymphocyte rolling in peripheral lymph nodes and showed a 53% reduction (P=0.0006) of lymphocyte rolling in mice treated with efomycine M or a function-blocking antibody against L-selectin. In addition, the number of lymph node-homing T cells was reduced by >60% using either efomycine M or L-selectin-blocking antibodies. As recruitment of naive lymphocytes is a prerequisite for sensitization in T-cell-mediated immune reactions and allergic responses, mice were treated with efomycine M or an L-selectin-specific antibody during contact sensitization with DNFB. After adoptive transfer of corresponding T cells into non-sensitized recipient mice, the capacity of these cells to induce contact hypersensitivity was significantly reduced (P=0.0002 and P=0.0001, respectively). Our data demonstrate that it is possible, in principle, to diminish T-cell-mediated allergic reactions through interference with L-selectin functions during the early sensitization phase.

Keywords
  • Adoptive Transfer
  • Animals
  • Antibodies/*pharmacology
  • Cell Adhesion
  • Cell Movement
  • Dermatitis, Contact/prevention & control
  • Humans
  • Hypersensitivity/*prevention & control
  • L-Selectin/immunology/*physiology
  • Lymphocytes/*physiology
  • Macrolides/*pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Shear Strength
Affiliation Not a UNIGE publication
Citation (ISO format)
OOSTINGH, Gertie J. et al. Diminished lymphocyte adhesion and alleviation of allergic responses by small-molecule- or antibody-mediated inhibition of L-selectin functions. In: Journal of investigative dermatology, 2007, vol. 127, n° 1, p. 90–97. doi: 10.1038/sj.jid.5700504
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ISSN of the journal0022-202X
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