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The Journal of Immunology, Vol 155, Issue 4 2158-2164, Copyright © 1995 by American Association of Immunologists

ARTICLES

Chemokine binding and activities mediated by the mouse IL-8 receptor

J Lee, G Cacalano, T Camerato, K Toy, MW Moore and WI Wood
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA.

In humans and rabbits two similar IL-8R mediate the chemotaxis and activation of neutrophils induced by alpha chemokines. We present data to suggest that there is only one such IL-8R gene in mice. We then use mice with a targeted deletion of this gene to characterize alpha chemokine ligands that signal via the mouse IL-8R. These experiments show that mouse macrophage inflammatory protein 2 binds the receptor with high affinity (Kd = approximately 1.5 nM) and potently activates both an intracellular Ca2+ flux and a chemotactic response, events absent in neutrophils from receptor-deleted mice. Mouse KC is approximately 10-fold less potent. These results show that macrophage inflammatory protein 2 and KC potently activate mouse neutrophils via a unique IL-8R, and these proteins may function as the major proinflammatory alpha chemokines in mice.


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