NEUTROPHIL AND B-CELL EXPANSION IN MICE THAT LACK THE MURINE IL-8 RECEPTOR HOMOLOG

Interleukin-8 (IL-8) is a preinflammatory cytokine that specifically a ttracts and activates human neutrophils. A murine gene with a high deg ree of homology to the two known human IL-8 receptors was cloned and t hen deleted from the mouse genome by homologous recombination in embry onic stem (ES) cells. These mice, although outwardly healthy, had lymp hadenopathy, resulting from an increase in B cells, and splenomegaly, resulting from an increase in metamyelocytes, band, and mature neutrop hils. Thus, this receptor may participate in the expansion and develop ment of neutrophils and B cells. This receptor was the major mediator of neutrophil migration to sites of inflammation and may provide a pot ential therapeutic target in inflammatory disease.