Impaired host defense in mice lacking ONZIN

JG Ledford, M Kovarova, BH Koller - The Journal of Immunology, 2007 - journals.aai.org
JG Ledford, M Kovarova, BH Koller
The Journal of Immunology, 2007journals.aai.org
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 …
Abstract
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.
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