Chemokine binding and activities mediated by the mouse IL-8 receptor.
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.
Lee
J
J
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA.
Cacalano
G
G
Camerato
T
T
Toy
K
K
Moore
M W
MW
Wood
W I
WI
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
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