Impaired host defense in mice lacking ONZIN.
ONZIN is a small, cysteine-rich peptide of unique structure that is conserved in all vertebrates examined to date. We show that ONZIN is expressed at high levels in epithelial cells of the intestinal tract, the lung, and in cells of the immune system including macrophages and granulocytes. Because this pattern of expression is suggestive of a role in innate immune function, we have generated mice lacking this protein and examined their ability to respond to challenge with infectious agents. Onzin(-/-) mice show a heightened innate immune response after induction of acute peritonitis with Klebsiella pneumoniae. This increased response is consistent with an increased bacterial burden in the Onzin(-/-) mice. Ex vivo studies show that, whereas phagocytosis is not altered in Onzin(-/-) neutrophils, phagocytes lacking this protein kill bacteria less effectively. This result identifies ONZIN as a novel class of intracellular protein required for optimal function of the neutrophils after uptake of bacteria.
Ledford
Julie G
JG
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
Kovarova
Martina
M
Koller
Beverly H
BH
D000595:Amino Acid Sequence; D000818:Animals; D001770:Blood Bactericidal Activity; D002118:Calcium / Q000378:metabolism; D007113:Immunity, Innate; D007710:Klebsiella Infections / Q000276:immunology; D007711:Klebsiella pneumoniae; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D015513:Oncogene Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D010538:Peritonitis / Q000276:immunology; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D011817:Rabbits; D016897:Respiratory Burst
D015513:Oncogene Proteins; D049294:Phospholipid Transfer Proteins; C506003:onzin protein, mouse; D002118:Calcium