Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis.

Published

Journal Article

Neutrophil elastase (NE) is a potent serine proteinase whose expression is limited to a narrow window during myeloid development. In neutrophils, NE is stored in azurophil granules along with other serine proteinases (cathepsin G, proteinase 3 and azurocidin) at concentrations exceeding 5 mM. As a result of its capacity to efficiently degrade extracellular matrix, NE has been implicated in a variety of destructive diseases. Indeed, while much interest has focused on the pathologic effects of this enzyme, little is known regarding its normal physiologic function(s). Because previous in vitro data have shown that NE exhibits antibacterial activity, we investigated the role of NE in host defense against bacteria. Generating strains of mice deficient in NE (NE-/-) by targeted mutagenesis, we show that NE-/- mice are more susceptible than their normal littermates to sepsis and death following intraperitoneal infection with Gram negative (Klebsiella pneumoniae and Escherichia coli) but not Gram positive (Staphylococcus aureus) bacteria. Our data indicate that neutrophils migrate normally to sites of infection in the absence of NE, but that NE is required for maximal intracellular killing of Gram negative bacteria by neutrophils.

Full Text

Duke Authors

Cited Authors

  • Belaaouaj, A; McCarthy, R; Baumann, M; Gao, Z; Ley, TJ; Abraham, SN; Shapiro, SD

Published Date

  • May 1998

Published In

Volume / Issue

  • 4 / 5

Start / End Page

  • 615 - 618

PubMed ID

  • 9585238

Pubmed Central ID

  • 9585238

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm0598-615

Language

  • eng