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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4282-4293
Normal Neutrophil Function in Cathepsin G-Deficient Mice
Debra M. MacIvor,
Steven D. Shapiro,
Christine T.N. Pham,
Abderazzaq Belaaouaj,
Soman N. Abraham, and
Timothy J. Ley
From the Departments of Internal Medicine and Genetics, Division of
Bone Marrow Transplantation and Stem Cell Biology, Department of
Pediatrics, Medicine, and Cell Biology, Division of Rheumatology, and
Department of Pathology, Washington University Medical School, St
Louis, MO.
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.
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