The intrinsic apoptotic pathway is required for lipopolysaccharide-induced lung endothelial cell death

Helena L. Wang, I. Ozkan Akinci, Christina M. Baker, Daniela Urich, Amy Bellmeyer, Manu Jain, Navdeep S. Chandel, Gökhan M. Mutlu, G. R.Scott Budinger

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

LPS has been implicated in the pathogenesis of endothelial cell death associated with Gram-negative bacterial sepsis. The binding of LPS to the TLR-4 on the surface of endothelial cells initiates the formation of a death-inducing signaling complex at the cell surface. The subsequent signaling pathways that result in apoptotic cell death remain unclear and may differ among endothelial cells in different organs. We sought to determine whether LPS and cycloheximide-induced cell death in human lung microvascular endothelial cells (HmVECs) was dependent upon activation of the intrinsic apoptotic pathway and the generation of reactive oxygen species. We found that cells overexpressing the anti-apoptotic protein Bcl-XL were resistant to LPS and cycloheximide-induced death and that the proapoptotic Bcl-2 protein Bid was cleaved following treatment with LPS. The importance of Bid was confirmed by protection of Bid-deficient (bid-/-) mice from LPS-induced lung injury. Neither HmVECs treated with the combined superoxide dismutase/catalase mimetic EUK-134 nor HmVECs depleted of mitochondrial DNA (ρ0 cells) were protected against LPS and cycloheximide-induced death. We conclude that LPS and cycloheximide-induced death in HmVECs requires the intrinsic cell death pathway, but not the generation of reactive oxygen species.

Original languageEnglish (US)
Pages (from-to)1834-1841
Number of pages8
JournalJournal of Immunology
Volume179
Issue number3
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The intrinsic apoptotic pathway is required for lipopolysaccharide-induced lung endothelial cell death'. Together they form a unique fingerprint.

Cite this