title: Chemokine binding and activities mediated by the mouse IL-8 receptor.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Cacalano
authors.forename: T
authors.initials: T
authors.lastname: Camerato
authors.forename: K
authors.initials: K
authors.lastname: Toy
authors.forename: M W
authors.initials: MW
authors.lastname: Moore
authors.forename: W I
authors.initials: WI
authors.lastname: Wood
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology*; D023062:Receptors, Interleukin-8A
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D016209:Interleukin-8; D015846:Monokines; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; C074302:keratinocyte-derived chemokines; D002118:Calcium