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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
Nieswandt, Bernhard
Tauber, Rudolf
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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 TransferAnimalsAntibodies/*pharmacologyCell AdhesionCell MovementDermatitis, Contact/prevention & controlHumansHypersensitivity/*prevention & controlL-Selectin/immunology/*physiologyLymphocytes/*physiologyMacrolides/*pharmacologyMiceMice, Inbred C57BLShear Strength
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PMID: 16902419
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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. https://archive-ouverte.unige.ch/unige:29861

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Deposited on : 2013-09-20

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