| First Author | Garantziotis S | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 6 | Pages | 4187-92 |
| PubMed ID | 17785858 | Mgi Jnum | J:152023 |
| Mgi Id | MGI:4355785 | Doi | 10.4049/jimmunol.179.6.4187 |
| Citation | Garantziotis S, et al. (2007) Inter-alpha-trypsin inhibitor attenuates complement activation and complement-induced lung injury. J Immunol 179(6):4187-92 |
| abstractText | 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. |
