Normal neutrophil function in cathepsin G-deficient mice.

Published

Journal Article

Cathepsin G is a neutral serine protease that is highly expressed at the promyelocyte stage of myeloid development. We have developed a homologous recombination strategy to create a loss-of-function mutation for murine cathepsin G. Bone marrow derived from mice homozygous for this mutation had no detectable cathepsin G protein or activity, indicating that no other protease in bone marrow cells has the same specificity. Hematopoiesis in cathepsin G-/- mice is normal, and the mice have no overt abnormalities in blood clotting. Neutrophils derived from cathepsin G-/- mice have normal morphology and azurophil granule composition; these neutrophils also display normal phagocytosis and superoxide production and have normal chemotactic responses to C5a, fMLP, and interleukin-8. Although cathepsin G has previously shown to have broad spectrum antibiotic properties, challenges of mice with Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli yielded survivals that were not different from those of wild-type animals. In sum, cathepsin G-/- neutrophils have no obvious defects in function; either cathepsin G is not required for any of these normal neutrophil functions or related azurophil granule proteases with different specificities (ie, neutrophil elastase, proteinase 3, azurocidin, and/or others) can substitute for it in vivo.

Full Text

Duke Authors

Cited Authors

  • MacIvor, DM; Shapiro, SD; Pham, CT; Belaaouaj, A; Abraham, SN; Ley, TJ

Published Date

  • December 15, 1999

Published In

Volume / Issue

  • 94 / 12

Start / End Page

  • 4282 - 4293

PubMed ID

  • 10590073

Pubmed Central ID

  • 10590073

International Standard Serial Number (ISSN)

  • 0006-4971

Language

  • eng

Conference Location

  • United States