Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog.
Interleukin-8 (IL-8) is a proinflammatory cytokine that specifically attracts and activates human neutrophils. A murine gene with a high degree of homology to the two known human IL-8 receptors was cloned and then deleted from the mouse genome by homologous recombination in embryonic stem (ES) cells. These mice, although outwardly healthy, had lymphadenopathy, resulting from an increase in B cells, and splenomegaly, resulting from an increase in metamyelocytes, band, and mature neutrophils. Thus, this receptor may participate in the expansion and development of neutrophils and B cells. This receptor was the major mediator of neutrophil migration to sites of inflammation and may provide a potential therapeutic target in inflammatory disease.
Cacalano
G
G
Department of Cell Genetics, Genentech, South San Francisco, CA 94080.
Lee
J
J
Kikly
K
K
Ryan
A M
AM
Pitts-Meek
S
S
Hultgren
B
B
Wood
W I
WI
Moore
M W
MW
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D002678:Chimera; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D007249:Inflammation / Q000276:immunology*; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology*; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D023063:Receptors, Interleukin-8B; D011995:Recombination, Genetic; D013154:Spleen / Q000473:pathology; D013234:Stem Cells
D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B