Inter-alpha-trypsin inhibitor attenuates complement activation and complement-induced lung injury.


Journal Article

Complement activation is a central component of inflammation and sepsis and can lead to significant tissue injury. Complement factors are serum proteins that work through a cascade of proteolytic reactions to amplify proinflammatory signals. Inter-alpha-trypsin inhibitor (IaI) is an abundant serum protease inhibitor that contains potential complement-binding domains, and has been shown to improve survival in animal sepsis models. We hypothesized that IaI can bind complement and inhibit complement activation, thus ameliorating complement-dependent inflammation. We evaluated this hypothesis with in vitro complement activation assays and in vivo in a murine model of complement-dependent lung injury. We found that IaI inhibited complement activation through the classical and alternative pathways, inhibited complement-dependent phagocytosis in vitro, and reduced complement-dependent lung injury in vivo. This novel function of IaI provides a mechanistic explanation for its observed salutary effects in sepsis and opens new possibilities for its use as a treatment agent in inflammatory diseases.

Full Text

Cited Authors

  • Garantziotis, S; Hollingsworth, JW; Ghanayem, RB; Timberlake, S; Zhuo, L; Kimata, K; Schwartz, DA

Published Date

  • September 2007

Published In

Volume / Issue

  • 179 / 6

Start / End Page

  • 4187 - 4192

PubMed ID

  • 17785858

Pubmed Central ID

  • 17785858

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.179.6.4187


  • eng