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

Oostingh, Gertie J.; Ludwig, Ralf J.; Enders, Sven; Gruner, Sabine; Harms, Gesche; Boehncke, Wolf-Henning; Nieswandt, Bernhard; Tauber, Rudolf; Schon, Michael P.

doi:10.1038/sj.jid.5700504

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Title		Diminished lymphocyte adhesion and alleviation of allergic responses by small-molecule- or antibody-mediated inhibition of L-selectin functions
Authors		Oostingh, Gertie J. Ludwig, Ralf J. Enders, Sven Gruner, Sabine Harms, Gesche Boehncke, Wolf-Henning Nieswandt, Bernhard Tauber, Rudolf Schon, Michael P. show all authors [1 - 9]
Published in		Journal of Investigative Dermatology. 2007, vol. 127, no. 1, p. 90-97
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
Identifiers		DOI: 10.1038/sj.jid.5700504 PMID: 16902419
Full text		Article - Limited access to UNIGE Other version: http://www.nature.com/jid/journal/v127/n1/pdf/5700504a.pdf
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 https://archive-ouverte.unige.ch/unige:29861