Normal neutrophil function in cathepsin G-deficient mice.
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.
MacIvor
D M
DM
Department of Internal Medicine, Division of Bone Marrow Transplantation and Stem Cell Biology, Washington University Medical School, St. Louis, MO 63110, USA.
Shapiro
S D
SD
Pham
C T
CT
Belaaouaj
A
A
Abraham
S N
SN
Ley
T J
TJ
D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000235:genetics*; D002634:Chemotaxis, Leukocyte; D017353:Gene Deletion; D006720:Homozygote; D051379:Mice; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis; D012697:Serine Endopeptidases / Q000502:physiology
D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse