Naslov
Inflammatory Potency of Monomeric Complex of Endotoxin With MD-2 is Determined by the Acylation State of Endotoxin

Autori
Hađina, Suzana, Weiss, Jerrold P., McCray, Paul B. Jr., Widstrom, Richard, Thorne, Peter S.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
American Journal of Respiratory and Critical Care Medicine, volume 175, Abstracts issue / - New York (NY) : American Thoracic Society (ATS), 2007

Skup
ATS 2007 International Conference

Mjesto i datum
San Francisco (CA), Sjedinjene Američke Države, 18.05.2007. - 23.05.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
N. meningitidis; endotoxin; monomeric complex

Sažetak
Rationale: Maximum host cell responsiveness to endotoxin requires at least four extracellular and cell surface host proteins (LBP, CD-14, MD-2 and TLR4). These proteins engage endotoxin in a series of protein-protein and protein-endotoxin interactions initiating a signal transduction cascade leading to the release of proinflammatory mediators. We sought to compare the ability of two different monomeric endotoxin:MD-2 complexes in inducing lung inflammatory responses. Methods: BALB/c mice were nasally instilled with monomeric complexes of penta- (LOSmsbB) and hexa-acylated (LOSwt) N. meningitidis endotoxin:MD-2 in doses of 0, 3, 30 and 300 EU/mouse. After 4 hours, mice were euthanized and processed for bronchoalveolar lavage (BAL). Concentration of MIP-1α , TNF-α , IL-6 and G-CSF were determined in BAL and lungs were evaluated for the accumulation of neutrophils. Results: At lower doses (3 and 30 EU/mouse) LOSmsbB:MD-2-induced inflammatory responses were markedly reduced compared with LOSwt:MD-2-treated mice in the number of BAL cells (2 to 10-fold) and concentration of IL-6, G-CSF (4 to 6-fold), TNF-α and MIP-1α (9 to 18-fold). At the higher dose (300 EU/mouse) the LOSwt:MD-2-treated group had 2-fold higher number of total cells, neutrophils and concentrations of TNF-α and G-CSF than LOSmsbB:MD-2, while IL-6 and MIP-1α reached similar levels in BAL. Conclusions: Differences in the intensity of lung inflammatory responses between two types of monomeric complexes of lipooligosaccharides with MD-2 reflected differences in the structure and bioactivity of hexa- and penta-acylated lipooligosaccharides. Complexes of endotoxin with MD-2 serve as ligands and activators of TLR-4 signaling and their activity in vivo can be modulated by using endotoxin species differing in fatty acid content. Funded By: NIH P30 ES05605

Izvorni jezik
Engleski

Znanstvena područja
Javno zdravstvo i zdravstvena zaštita, Veterinarska medicina

POVEZANOST RADA